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C10orf90, a tumor suppressor, can inhibit the occurrence and development of tumors. Therefore, we investigated the gene function of C10orf90 in various tumors using multiple pan-cancer datasets. Pan-cancer analysis results reveal that the expression levels of C10orf90 vary across different tumors and hold significant value in the clinical diagnosis and prognosis of patients with various tumors. In some cancers, the expression level of C10orf90 is correlated with CNV, DNA methylation, immune subtypes, immune cell infiltration, and drug sensitivity in the tumors. In particular, in COAD, the C10orf90 gene is implicated in multiple processes associated with COAD. Cell experiments demonstrate that C10orf90 suppresses the proliferation and migration of colon cancer cells while promoting apoptosis. In summary, C10orf90 plays a role in the onset and progression of various cancers and could potentially serve as an effective diagnostic and prognostic marker for cancer patients. Notably, in COAD, C10orf90 inhibits the proliferation and migration of colon cancer cells, induces apoptosis, and is linked to the advancement of colon cancer. [ABSTRACT FROM AUTHOR]

Abstract Purpose Metabolic reprogramming is a hallmark of cancer and plays a key role in precision oncology treatment. Long non-coding RNAs (lncRNAs) regulate cancer cell behavior, including metabolism. Disulfidptosis, a newly identified form of regulated cell death triggered by glucose starvation, has yet to be fully understood in colon adenocarcinoma (COAD). This study aimed to confirm the existence and role of disulfidptosis in COAD and identify disulfidptosis-related lncRNAs that may be targeted to induce disulfidptosis in COAD. Methods PI and F-actin staining were used to observe disulfidptosis in COAD cell lines. Disulfidptosis-related lncRNAs were identified based on the expression of disulfidptosis-associated genes in the TCGA-COAD database. A four-lncRNA signature for disulfidptosis was established. Subsequently, loss-of-function assays explored the roles of AC013652.1 and MCM3AP-AS1 in disulfidptosis. Results Disulfidptosis was observed in COAD cells under glucose starvation and could be reversed by agents that prevent disulfide stress, such as dithiothreitol (DTT) and tris-(2-carboxyethyl)-phosphine (TCEP). The prognostic value of disulfidptosis-associated genes in COAD patients was confirmed, with higher expression indicating longer survival. A disulfidptosis-related lncRNA signature comprising four lncRNAs was established based on the expression of these genes. Among these, AC013652.1 and MCM3AP-AS1 predicted worse prognoses. Furthermore, inhibiting AC013652.1 or MCM3AP-AS1 increased disulfidptosis-associated gene expression and cellular death, which could be reversed by DTT and TCEP. Conclusions This study provides hitherto undocumented evidence of the existence of disulfidptosis and the prognostic value of disulfidptosis-associated genes in COAD. Importantly, we identified lncRNAs AC013652.1 and MCM3AP-AS1, which suppress disulfidptosis and may serve as potential therapeutic targets for COAD.

Houxi Xu,1,2,* Hongqun Zhang,1,3,* Songxian Sun,2,* Jingyuan Zhang,2 Jiege Huo,1,3 Chunxiang Zhou2 1Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing, University of Chinese Medicine, Nanjing, People’s Republic of China; 2School of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 3The Third School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunxiang Zhou, School of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China, Email chunxiangzhou@njucm.edu.cn Jiege Huo, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People’s Republic of China, Email huojiege@jsatcm.comBackground: The CD1A gene, a key component of the human immune system and part of the CD1 family, plays a crucial role in presenting lipid antigens to T cells. Abnormal CD1A expression is associated with various immune-related diseases and tumors. However, the biological function of CD1A in COAD is unclear.Methods: Multiple databases were systematically employed to conduct an analysis of CD1A expression in pan-cancer and COAD, along with its clinical-pathological features. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses of CD1A were performed using the ‘clusterProfiler’ package. The Protein-protein interaction (PPI) analysis of CD1A was used the STRING database. Additionally, TIMER and ssGSEA tools were used to explore the relationship between CD1A expression in COAD and immune cell infiltration. The study also investigated the association between CD1A expression and N6-methyladenosine (m6A) modification genes in the TCGA COAD cohort and constructed a CD1A-centric competing endogenous RNA (ceRNA) regulatory network.Results: CD1A displays varying expression levels in various tumors, including COAD, and is closely linked to clinical-pathological characteristics. GO analysis suggests that CD1A plays a role in important processes like antigen processing and presentation, leukocyte-mediated immunity, and lymphocyte-mediated immunity. KEGG analysis identifies CD1A’s involvement in key pathways such as the Chemokine signaling pathway and Cytokine-cytokine receptor interaction. PPI analysis highlights CD1A’s interactions with CD207, CD1C, CD1E, FOXP3, and ITGB2. ssGSEA analysis indicates a significant relationship between CD1A expression and the infiltration of various immune cells in COAD. Significant associations were found between CD1A and m6A modification genes in COAD. Furthermore, a CD1A-centered ceRNA regulatory network has been constructed.Conclusion: CD1A emerges as a potential biomarker for the diagnosis and treatment of COAD, showing a strong association with tumor immune infiltration, m6A modification, and the ceRNA network.Keywords: CD1A, COAD, immune infiltration, m6A, ceRNA

Houxi Xu,1,2,* Hongqun Zhang,1,3,* Songxian Sun,2 Jingyuan Zhang,2 Jiege Huo,1,3 Chunxiang Zhou2 1Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2School of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing People’s Republic of China; 3The Third School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunxiang Zhou, School of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China, Email chunxiangzhou@njucm.edu.cn Jiege Huo, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People’s Republic of China, Email huojiege@jsatcm.comBackground: An increasing corpus of evidence has identified the involvement of N-acetyltransferase 1 (NAT1), a member of the NAT family, in the progression of various cancers. However, the specific function of NAT1 in colon cancer (COAD) remains elusive. This study aims to decip her the role of NAT1 in COAD and its associated mechanisms.Methods: The Tumor Immunity Evaluation Resource (TIMER), The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO) databases were employed to assess the NAT1 expression level in COAD. The differential expression between COAD and normal colon tissue was further validated using quantitative real-time reverse-transcription PCR (RT-qPCR) and Western blot (WB) analyses. Additionally, survival analysis of NAT1 in COAD was carried out using the PrognoScan database and TCGA dataset. The functions of NAT1 were explored through gene set enrichment analysis (GSEA) and immuno-infiltration analysis.Results: There was a significant reduction in NAT1 expression in COAD samples compared to normal tissue. Notably, low NAT1 expression in COAD correlated significantly with various clinical parameters such as tumor stage (T stage, N stage, M stage, pathologic stage), primary therapy outcome, carcinoembryonic antigen (CEA) level, and lymphatic invasion. The downregulation of NAT1 was also strongly linked with poor outcomes in overall survival (OS), progression-free interval (PFI), and disease-specific survival (DSS). Cox regression analysis highlighted NAT1 as an independent prognostic indicator for overall survival in COAD patients. GSEA results revealed NAT1’s involvement in multiple pathways, including the neuroactive ligand-receptor interaction, olfactory transduction, olfactory signaling, extracellular matrix receptor interaction, calcium signaling, and focal adhesion pathways. Furthermore, NAT1 expression was found to significantly correlate with infiltration levels of various immune cells.Conclusion: The findings reveal NAT1’s potential as a valuable prognostic biomarker for COAD. Moreover, its associated mechanisms offer insights that might pave the way for therapeutic interventions for COAD patients.Keywords: NAT1, COAD, prognosis, immune infiltration, RT-qPCR, western blot

Purpose: Metabolic reprogramming is a hallmark of cancer and plays a key role in precision oncology treatment. Long non-coding RNAs (lncRNAs) regulate cancer cell behavior, including metabolism. Disulfidptosis, a newly identified form of regulated cell death triggered by glucose starvation, has yet to be fully understood in colon adenocarcinoma (COAD). This study aimed to confirm the existence and role of disulfidptosis in COAD and identify disulfidptosis-related lncRNAs that may be targeted to induce disulfidptosis in COAD. Methods: PI and F-actin staining were used to observe disulfidptosis in COAD cell lines. Disulfidptosis-related lncRNAs were identified based on the expression of disulfidptosis-associated genes in the TCGA-COAD database. A four-lncRNA signature for disulfidptosis was established. Subsequently, loss-of-function assays explored the roles of AC013652.1 and MCM3AP-AS1 in disulfidptosis. Results: Disulfidptosis was observed in COAD cells under glucose starvation and could be reversed by agents that prevent disulfide stress, such as dithiothreitol (DTT) and tris-(2-carboxyethyl)-phosphine (TCEP). The prognostic value of disulfidptosis-associated genes in COAD patients was confirmed, with higher expression indicating longer survival. A disulfidptosis-related lncRNA signature comprising four lncRNAs was established based on the expression of these genes. Among these, AC013652.1 and MCM3AP-AS1 predicted worse prognoses. Furthermore, inhibiting AC013652.1 or MCM3AP-AS1 increased disulfidptosis-associated gene expression and cellular death, which could be reversed by DTT and TCEP. Conclusions: This study provides hitherto undocumented evidence of the existence of disulfidptosis and the prognostic value of disulfidptosis-associated genes in COAD. Importantly, we identified lncRNAs AC013652.1 and MCM3AP-AS1, which suppress disulfidptosis and may serve as potential therapeutic targets for COAD. [ABSTRACT FROM AUTHOR]

Chemokines are key proteins that regulate cell migration and immune responses and are essential for modulating the tumor microenvironment. Despite their close association with colon cancer, the expression patterns, prognosis, immunity, and specific roles of chemokines in colon cancer are still not fully understood. In this study, we investigated the mutational features, differential expression, and immunological characteristics of chemokines in colon cancer (COAD) by analyzing the Tumor Genome Atlas (TCGA) database. We clarified the biological functions of these chemokines using Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. By univariate and multivariate COX regression analyses, we developed chemokine-based prognostic risk models. In addition, using Gene Set Enrichment Analysis (GSEA) and Gene Set Variant Analysis (GSVA), we analyzed the differences in immune responses and signaling pathways among different risk groups. The results showed that the mutation rate of chemokines was low in COAD, but 25 chemokines were significantly differentially expressed. These chemokines function in several immune-related biological processes and play key roles in signaling pathways including cytokine–cytokine receptor interactions, NF-kappa B, and IL-17. Prognostic risk models based on CCL22, CXCL1, CXCL8, CXCL9, and CXCL11 performed well. GSEA and GSVA analyses showed significant differences in immune responses and signaling pathways across risk groups. In conclusion, this study reveals the potential molecular mechanisms of chemokines in COAD and proposes a new prognostic risk model based on these insights. [ABSTRACT FROM AUTHOR]

Phosphopantetheine adenylyltransferase (EC. 2.7.7.3, PPAT) catalyzes the penultimate step of the multistep reaction in the coenzyme A (CoA) biosynthesis pathway. In this step, an adenylyl group from adenosine triphosphate (ATP) is transferred to 4′-phosphopantetheine (PNS) yielding 3′-dephospho-coenzyme A (dpCoA) and pyrophosphate (PPi). PPAT from strain C3 of Klebsiella pneumoniae (KpPPAT) was cloned, expressed and purified. It was crystallized using 0.1 M HEPES buffer and PEG10000 at pH 7.5. The crystals belonged to tetragonal space group P41212 with cell dimensions of a = b = 72.82 Å and c = 200.37 Å. The structure was determined using the molecular replacement method and refined to values of 0.208 and 0.255 for Rcryst and Rfree factors, respectively. The structure determination showed the presence of three crystallographically independent molecules A, B and C in the asymmetric unit. The molecules A and B are observed in the form of a dimer in the asymmetric unit while molecule C belongs to the second dimer whose partner is related by crystallographic twofold symmetry. The polypeptide chain of KpPPAT folds into a β/α structure. The conformations of the side chains of several residues in the substrate binding site in KpPPAT are significantly different from those reported in other PPATs. As a result, the modes of binding of substrates, phosphopantetheine (PNS) and adenosine triphosphate (ATP) differ considerably. The binding studies using fluorescence spectroscopy indicated a KD value of 3.45 × 10−4 M for ATP which is significantly lower than the corresponding values reported for PPAT from other species. [ABSTRACT FROM AUTHOR]

C10orf90, a tumor suppressor, can inhibit the occurrence and development of tumors. Therefore, we investigated the gene function of C10orf90 in various tumors using multiple pan-cancer datasets. Pan-cancer analysis results reveal that the expression levels of C10orf90 vary across different tumors and hold significant value in the clinical diagnosis and prognosis of patients with various tumors. In some cancers, the expression level of C10orf90 is correlated with CNV, DNA methylation, immune subtypes, immune cell infiltration, and drug sensitivity in the tumors. In particular, in COAD, the C10orf90 gene is implicated in multiple processes associated with COAD. Cell experiments demonstrate that C10orf90 suppresses the proliferation and migration of colon cancer cells while promoting apoptosis. In summary, C10orf90 plays a role in the onset and progression of various cancers and could potentially serve as an effective diagnostic and prognostic marker for cancer patients. Notably, in COAD, C10orf90 inhibits the proliferation and migration of colon cancer cells, induces apoptosis, and is linked to the advancement of colon cancer.

Abstract Colon adenocarcinoma (COAD) is one of the most frequent types of cancer worldwide. Disulfidptosis has been identified as a new mode of cell death recently. The goal of this study was to explore the possibility of a connection between disulfidptosis and COAD. RNA sequencing data from COAD patients were retrieved from the The Cancer Genome Atlas (TCGA) database for this investigation. R software and various methods were used to identify disulfidptosis-related lncRNAs (DRLs) in COAD, and a prognostic model was created based on 6 DRLs (AP003555.1, AL683813.1, SNHG7, ZEB1-AS1, AC074212.1, RPL37A-DT). The prognostic model demonstrated a good accuracy in predicting the prognosis of COAD patients, according to receiver operating characteristic (ROC) curve and Concordance index (C-index) analyses. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed significant differences in biological functions and signaling pathways involved in differential genes in risk subgroups, including protein − DNA complex subunit organization, Hippo signaling pathway, Wnt signaling pathway. TIDE analysis was done on risk groupings in this study, and it found that patients in the high-risk group had more immune escape potential and were less probable to react to immunotherapy. Real-time quantitative pcr (qRT-PCR) was used to identify the relatively high expression of 6 DRLs in colon cancer cell lines. In summary, 6 DRLs were identified as possible novel molecular therapy targets for COAD in this investigation. This prognostic model has the potential to be a novel tool for forecasting COAD prognosis in clinical practice, as well as providing new insights on the potential function and mechanism of disulfidptosis in the COAD process.

Abstract Background Several proteins in the tripartite-motif (TRIM) family are associated with the development of colorectal cancer (CRC), but research on the role of TRIM69 was lacking. The present study examined the correlation between TRIM69 expression and colon adenocarcinoma (COAD). Methods mRNA sequencing data for COAD patients was extracted from The Cancer Genome Atlas to analyze correlations between TRIM69 expression and patients’ clinical features as well as survival. Potential associations with immune cells and chemosensitivity also were predicted using various algorithms in the TIMER, Limma, clusterProfiler, GeneMANIA, and Gene Set Cancer Analysis platforms. Subsequently, polymerase chain reaction analysis and immunohistochemical staining were used to detect TRIM69 expression in COAD tissue samples from real-world patients. Results TRIM69 expression was lower in COAD tissues than in normal tissues and correlated with the pathologic stage and metastasis (M category). Additionally, TRIM69 was found to be involved in several immune-related pathways, notably the NOD-like signaling pathway. These results suggest that high TRIM69 expression has the potential to enhance tumor sensitivity to 5-fluorouracil and programmed cell death protein 1 (PD-1) blockers. Conclusions From our findings that TRIM69 expression was significantly reduced in COAD compared with non-cancer tissues and associated with pathologic stage and metastasis, we conclude that increasing TRIM69 expression and/or activity may help to improve therapeutic outcomes. Accordingly, TRIM69 represents a potentially valuable marker of metastasis and target for adjuvant therapy in COAD.

Background: Colon adenocarcinoma (COAD) is a prevalent malignancy worldwide, yet, its underlying pathogenesis and genetic characteristics are still unclear. Previous studies have suggested that NADH dehydrogenase 1 alpha subcomplex subunit 4-like 2 (NDUFA4L2) may affect tumor progression across various cancers. However, this effect on COAD has rarely been reported. Thus, this study investigated NDUFA4L2's prognostic and diagnostic relevance and explored its potential connection with immune cell infiltration in COAD. Methods: To achieve this, RNA sequencing data from Cancer Genome Atlas (TCGA) was analyzed to assess NDUFA4L2's prognostic value in COAD, and factors relevant to the prognosis of COAD, including NDUFA4L2, were scrutinized using Kaplan-Meier analyses as well as univariate and multivariate Cox regression. A nomogram model was created to project prognosis based on the results of multivariate Cox analysis. Furthermore, gene set enrichment analysis (GSEA) was employed to pinpoint key NDUFA4L2-related pathways, and single-sample GSEA (ssGSEA) on TCGA data was employed to investigate the connections of NDUFA4L2 with cancer immune infiltrations. Results: Our findings revealed significant associations of high NDUFA4L2 expression with poor overall survival, progression-free interval, and disease-specific survival of COAD patients. GSEA indicated close links of NDUFA4L2 with several signaling pathways implicated in tumorigenesis, including extracellular matrix receptor interaction, the intestinal immune network for immunoglobulin A production, natural killer (NK) cell-mediated cytotoxicity, pathways in cancer, cell adhesion molecules, mitogen-activated protein kinase signaling pathway, Hedgehog signaling pathway, transforming growth factor beta signaling pathway, and chemokine signaling pathway. Additionally, ssGSEA identified a positive link between increased NDUFA4L2 expression and higher infiltration degree of various immune cells, such as immature dendritic cells, macrophages, NK cells and dendritic cells. Conclusions: Collectively, our findings demonstrate the association of increased NDUFA4L2 expression with adverse prognosis and heightened immune cell infiltration in COAD patients.

Regenerating family protein 3 A (Reg3A) is highly expressed in a variety of organs and inflammatory tissues, and is closely related to tumorigenesis and cancer progression. However, clinical statistics show that high expression of Reg3A is associated with better prognosis in colorectal cancer (CRC) patients, suggesting a tumor-suppressive effect. The precise action and underlying mechanism of Reg3A in CRC remain controversial. The present study sought to investigate the relationship among Reg3A expression, CRC development, and immune cell alteration in patients using the TCGA, GEPIA, PrognoScan, TIMER and TISIDB databases. Reg3A-overexpressing LoVo cell line (LoVo-Reg3A), a representative of colon adenocarcinoma (COAD), was constructed and the action of Reg3A was assessed in a xenograft nude mouse model. Our bioinformatical analyses revealed that Reg3A upregulation is highly associated with CRC, along with increased frequency of immune cell infiltration. In the xenograft nude mice, Reg3A overexpression offered a tumor-suppressive effect by inhibiting cell proliferation and promoting apoptosis. The result of RNA-seq suggested a positive regulation of leukocytes and an upregulation of T cells in LoVo-Reg3A tumor tissue. CD4+ and CD8+ T cells in tumors, splenic Reg3A-reactive IFN-γ+/CD4+ T cells, and serum TNF-α, IFN-γ and IL-17 were significantly increased by Reg3A overexpression. In the ex vivo co-culture experiment, elevated cytotoxic effect, increased proportion of CD3ε+ T cells, and upregulated expressions of TNF-α, IFN-γ and IL-17 were detected in the PBMCs isolated from LoVo-Reg3A cell-xenografted nude mice. In conclusion, high expression of Reg3A could activate and recruit T cells in COAD leading to the cytotoxic tumor-suppressive effect.

Colon adenocarcinoma (COAD) is one of the most frequent types of cancer worldwide. Disulfidptosis has been identified as a new mode of cell death recently. The goal of this study was to explore the possibility of a connection between disulfidptosis and COAD. RNA sequencing data from COAD patients were retrieved from the The Cancer Genome Atlas (TCGA) database for this investigation. R software and various methods were used to identify disulfidptosis-related lncRNAs (DRLs) in COAD, and a prognostic model was created based on 6 DRLs (AP003555.1, AL683813.1, SNHG7, ZEB1-AS1, AC074212.1, RPL37A-DT). The prognostic model demonstrated a good accuracy in predicting the prognosis of COAD patients, according to receiver operating characteristic (ROC) curve and Concordance index (C-index) analyses. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed significant differences in biological functions and signaling pathways involved in differential genes in risk subgroups, including protein − DNA complex subunit organization, Hippo signaling pathway, Wnt signaling pathway. TIDE analysis was done on risk groupings in this study, and it found that patients in the high-risk group had more immune escape potential and were less probable to react to immunotherapy. Real-time quantitative pcr (qRT-PCR) was used to identify the relatively high expression of 6 DRLs in colon cancer cell lines. In summary, 6 DRLs were identified as possible novel molecular therapy targets for COAD in this investigation. This prognostic model has the potential to be a novel tool for forecasting COAD prognosis in clinical practice, as well as providing new insights on the potential function and mechanism of disulfidptosis in the COAD process. [ABSTRACT FROM AUTHOR]

Chemokines are key proteins that regulate cell migration and immune responses and are essential for modulating the tumor microenvironment. Despite their close association with colon cancer, the expression patterns, prognosis, immunity, and specific roles of chemokines in colon cancer are still not fully understood. In this study, we investigated the mutational features, differential expression, and immunological characteristics of chemokines in colon cancer (COAD) by analyzing the Tumor Genome Atlas (TCGA) database. We clarified the biological functions of these chemokines using Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. By univariate and multivariate COX regression analyses, we developed chemokine-based prognostic risk models. In addition, using Gene Set Enrichment Analysis (GSEA) and Gene Set Variant Analysis (GSVA), we analyzed the differences in immune responses and signaling pathways among different risk groups. The results showed that the mutation rate of chemokines was low in COAD, but 25 chemokines were significantly differentially expressed. These chemokines function in several immune-related biological processes and play key roles in signaling pathways including cytokine–cytokine receptor interactions, NF-kappa B, and IL-17. Prognostic risk models based on CCL22, CXCL1, CXCL8, CXCL9, and CXCL11 performed well. GSEA and GSVA analyses showed significant differences in immune responses and signaling pathways across risk groups. In conclusion, this study reveals the potential molecular mechanisms of chemokines in COAD and proposes a new prognostic risk model based on these insights.

Background: Several proteins in the tripartite-motif (TRIM) family are associated with the development of colorectal cancer (CRC), but research on the role of TRIM69 was lacking. The present study examined the correlation between TRIM69 expression and colon adenocarcinoma (COAD). Methods: mRNA sequencing data for COAD patients was extracted from The Cancer Genome Atlas to analyze correlations between TRIM69 expression and patients' clinical features as well as survival. Potential associations with immune cells and chemosensitivity also were predicted using various algorithms in the TIMER, Limma, clusterProfiler, GeneMANIA, and Gene Set Cancer Analysis platforms. Subsequently, polymerase chain reaction analysis and immunohistochemical staining were used to detect TRIM69 expression in COAD tissue samples from real-world patients. Results: TRIM69 expression was lower in COAD tissues than in normal tissues and correlated with the pathologic stage and metastasis (M category). Additionally, TRIM69 was found to be involved in several immune-related pathways, notably the NOD-like signaling pathway. These results suggest that high TRIM69 expression has the potential to enhance tumor sensitivity to 5-fluorouracil and programmed cell death protein 1 (PD-1) blockers. Conclusions: From our findings that TRIM69 expression was significantly reduced in COAD compared with non-cancer tissues and associated with pathologic stage and metastasis, we conclude that increasing TRIM69 expression and/or activity may help to improve therapeutic outcomes. Accordingly, TRIM69 represents a potentially valuable marker of metastasis and target for adjuvant therapy in COAD. [ABSTRACT FROM AUTHOR]

Background: Colon adenocarcinoma (COAD) is the second leading cause of cancer death worldwide thus, identification of COAD biomarkers is critical. Mitotic Arrest Deficient 2 Like 2 (MAD2L2) is a key factor in mammalian DNA damage repair and is highly expressed in many malignant tumors. This is a comprehensive study of MAD2L2 expression, its diagnostic value, prognostic analysis, potential biological function, and impact on the immune system of patients with COAD. Methods: Gene expression, clinical relevance, prognostic analysis, diagnostic value, GO/KEGG cluster analysis, data obtained from TCGA, and bioinformatics statistical analysis were performed using the R package. Immune responses to MAD2L2 expression in COAD were analyzed using TIMER. The expression of MAD2L2 in HCT116 cells induced by the inflammatory factor TNF-α was detected using Western blot. Results: Our results underscore the clinical diagnostic value and potential biological significance of MAD2L2 in patients with COAD. A high level of MAD2L2 expression has been found in COAD and correlated with tumor status and colon polyps. ROC curve analysis showed that MAD2L2 expression has high diagnostic value in COAD. Analysis of immune infiltration results showed that MAD2L2 expression was positively correlated with neutrophil levels. The western blot results demonstrated that MAD2L2 was dose-dependently present with TNF-α. GO/KEGG revealed that MAD2L2 overexpressed and coexpressed genes were mostly involved in biological functions, including hypoxia response, response to reduced oxygen levels, mitochondrial translation elongation, and other processes. Conclusion: MAD2L2 as a new COAD biomarker contributes to our understanding of how alterations in gene expression and the immunological environment contribute to the development of colon cancer. Following further investigation, MAD2L2 may prove to be a viable target factor for clinical diagnosis and therapy of COAD. [ABSTRACT FROM AUTHOR]

Introduction: Abnormal expression of integrin subunit beta 3 (ITGβ3), a geneencoding protein, is related to the occurrence and development of cancers; however, the biological role of ITGb3 in colon adenocarcinoma (COAD) remains unclear. Methods: We used the Cancer Genome Atlas database to obtain the clinical data of patients with COAD, analyzed the mRNA gene clusters related to ITGβ3, and analyzed the interaction signal pathway and interaction protein network of the differentially expressed gene clusters. The results showed that ITGβ3 expression in COAD tumor tissues was significantly downregulated compared with that in paracancerous tissues. Low ITGβ3 expression in tumor tissues is associated with poor overall survival of patients with COAD. In multivariate analysis, stage IV and ITGβ3 low expression were independent prognostic factors. Gene Ontology analysis showed that differentially expressed genes (DEGs) were significantly enriched in leukocyte migration, cell adhesion, and extracellular matrix (ECM) organization. Kyoto Encyclopedia of Genes and Genomes analysis revealed that the DEGs were mainly enriched in ECM-receptor interactions, focal adhesion, and the PI3K-Akt signaling pathway. Protein-protein interaction network analysis revealed the hub and seed genes of the key modules related to ITGβ3. Finally, we analyzed the correlation between TGβ3 and immune-related genes and found that ITGβ3 expression was significantly correlated with tumor purity and infiltration level of dominant immune cells. Discussion: These findings indicate that ITGβ3 downregulation in COAD may profoundly affect genome stability and multiple steps of the cell cycle, alter the tumor immune microenvironment, and be related to the prognosis of patients with COAD. [ABSTRACT FROM AUTHOR]

Background: Cuproptosis induced by FDX1 is a newly discovered mechanism regulating cell death. However, the role of FDX1 in the pathogenesis of colon adenocarcinoma (COAD) remains to be studied. Methods: FDX1 expression was analyzed with The Cancer Genome Atlas (TCGA) database and Human Protein Atlas (HPA) database. Association between FDX1 expression and COAD prognosis was investigated via the Kaplan–Meier (KM) survival curve. The differentially expressed genes (DEGs) of FDX1 were screened with R packages and the PPI were constructed via STRING database. Cytoscape software was used to detect the most profound modules in the PPIs network. CancerSEA database was used to analyze the effect of FDX1 expression levels on different functional status of COAD cells. The relationship between FDX1 expression and immune infiltration of COAD was analyzed by TIMER2.0 database. The COAD patients with high expression of FDX1 by Western blot, and the levels of immune infiltration were measured by flow cytometry. Results: FDX1 was low expressed in most cancers, such as BRCA, KICH, and COAD. The overall survival (OS) and disease-specific survival (DSS) of COAD with high FDX1 expression were better than that of the low expression group. GO-KEGG enrichment analysis revealed that FDX1 and its co-expressed genes played an important role in the pathogenesis of COAD. Moreover, FDX1 expression in COAD were positively associated with "quiescence" and "inflammation" but negatively correlated with "invasion". FDX1 expression was positively correlated with infiltration levels of CD8+ T cells, NK cells, and neutrophils. Oppositely, FDX1 expression was negatively correlated with that of CD4+ T cells and cancer-associated fibroblasts (CAFs). Finally, 6 COAD patients with high expression of FDX1 were screened, and the proportion of CD8+ T cells in cancer tissues of these patients was significantly higher than that in paracancerous, while the CD4+ T cells presented the opposite pattern. Conclusion: FDX1 plays a role in inducing cuproptosis and modulating tumor immunity, which could be considered as potential therapeutic targets in COAD. [ABSTRACT FROM AUTHOR]

Abstract Background MICAL-like protein 2 (MICAL-L2), a member of the molecules interacting with CasL (MICAL) family of proteins, is strongly associated with the malignancy of multiple types of cancer. However, the role of MICAL-L2 in colon adenocarcinoma (COAD) has not been well characterized. Methods In this study, we analyzed the role of MICAL-L2 in COAD using datasets available from public databases. The mRNA and protein expression of MICAL-L2 was investigated using TCGA, UALCAN, and independent immunohistochemical assays. Overall survival (OS) and disease-specific survival (DSS) of COAD patients were assessed based on the MICAL-L2 expression level using the Kaplan–Meier method. Univariate and multivariate analysis was employed to determine whether MICAL-L2 could serve as an independent prognostic indicator of OS. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were further utilized to explore the possible cellular mechanism underlying the role of MICAL-L2 in COAD. In addition, the correlation between MICAL-L2 expression and immune cell infiltration levels was investigated via single-sample gene set enrichment analysis (ssGSEA). Results Data from TCGA, HPA, and UALCAN datasets indicated that MICAL-L2 expression was significantly higher in COAD tissue than in adjacent normal tissues, and this was confirmed by immunohistochemical assays. Kaplan–Meier survival analysis revealed that patients with MICAL-L2 had shorter OS and DSS. Furthermore, multivariate Cox analysis indicated that MICAL-L2 was an independent risk factor for OS in COAD patients. ROC analysis confirmed the diagnostic value of MICAL-L2, and a prognostic nomogram involving age, M stage, and MICAL-L2 expression was constructed for OS. Functional enrichment analyses revealed that transport-related activity was closely associated with the role of MICAL-L2 in COAD. Regarding immune infiltration levels, MICAL-L2 was found to be positively associated with CD56bright NK cells. Conclusions Our results suggested that MICAL-L2 is a promising biomarker for determining prognosis and correlated with immune infiltration levels in COAD.

Abstract Background Colon adenocarcinoma (COAD) is one of the common cancers worldwide. Collagen triple helix repeat containing 1 (CTHRC1) has been reported to be involved in cell invasion, angiogenesis, and the promotion of epithelial-mesenchymal transformation by mediating multiple signaling pathways. However, the role of CTHRC1 in COAD has not yet been determined. Methods Differentially expressed genes were evaluated using gene expression data from the Oncomine and TIMER databases. Correlations between CTHRC1 gene expression and clinicopathological factors were analyzed using gene expression data from UALCAN databases. Then, we searched the GEPIA database to evaluate the association of CTHRC1 gene expression with clinical outcomes. The cBioPortal database was used to analyze CTHRC1 genetic alterations. Subsequently, the TIMER website was chosen to assess the correlation of CTHRC1 with the tumor immune cell infiltration level. The TCGA dataset was used for a gene set enrichment analysis (GSEA). Result CTHRC1 was highly expressed in COAD patients, and significantly related to poor prognosis. In addition, elevated expression of CTHRC1 was related to the clinical stage and pathological type of COAD. The GSEA analysis showed that CTHRC1 was enriched in Gα signaling, GCPR ligand binding, neutrophil degranulation, interleukin signaling, and tumor-associated pathways. In addition, CTHRC1 was significantly associated with the expression of multiple immune markers related to specific immune cells. Conclusion This study suggest that CTHRC1 expression is related to the prognosis and immune infiltration of COAD patients. Therefore, CTHRC1 may be a new candidate prognostic biomarker for determining immune infiltration levels and providing COAD prognoses.

Colon adenocarcinoma (COAD) is a malignant tumor with a high mortality rate. Angiogenesis plays a key role in the development and progression of cancer. However, in COAD, studies between angiogenesis and prognosis, immune cell infiltration, and personalized treatment guidance are currently lacking. In the present study, we comprehensively assessed 35 angiogenesis-related genes (ARG) and identified key ARGs affecting OS in COAD patients. The ARG Prognostic Index (ARGPI) was constructed based on a univariate Cox regression model and its prognostic value was evaluated in TCGA-COAD, GSE39582, GSE161158 and TRSJTUSM Cohort. We constructed ARGPI as an independent risk factor for OS in COAD patients and combined with clinical parameters to further construct an ARGPI-based nomogram, which showed a strong ability to predict overall survival in COAD patients. High ARGPI is associated with cancer-related and immune-related biological processes and signaling pathways; high TP53 mutation rate; high infiltration of MSC, pericytes, and stromal cells; and more CMS4 subtype. And low ARGPI benefited more from immune checkpoint inhibitor treatment. In addition, we also predicted the sensitivity of different ARGPI groups to common chemotherapeutic and targeted agents. In conclusion, this study constructed an ARGPI based on ARG, which robustly predicted the OS of COAD patients and provided a possible personalized treatment regime for COAD patients. [ABSTRACT FROM AUTHOR]

CUL7, a gene composed of 26 exons associated with cullin 7 protein, is also an E3 ligase that is closely related to cell senescence, apoptosis, and cell transformation and also plays an important role in human cancer. However, there is no systematic pan-cancer analysis has been performed to explore its role in prognosis and immune prediction. In this study, the expression of CUL7 in colon adenocarcinoma (COAD) was investigated to determine its prognosis value. First, based on the Cancer Genome Atlas (TCGA), Genotypic-Tissue Expression Project(GTEx), Cancer Cell Line Encyclopedias(CCLE), and TISIDB database, the potential role of CUL7 in different tumors was explored. Subsequently, the expression of CUL7 in COAD was explored and verified by Immunohistochemistry (IHC). Furthermore, the mutation frequency of CUL7 in COAD was analyzed, and the prognostic value of CUL7 in COAD was discussed. In addition, the nomogramwas constructed, and its prognostic value was verified by follow-up data from Jiangmen Central Hospital. Finally, PPI network analysis explored the potential biological function of CUL7 in COAD. The results show that CUL7 is upregulated in most tumors, which is significantly associated with poor survival. At the same time, CUL7 is correlated with the clinical stage and immune landscape of various tumors. In colorectal cancer, CUL7 was overexpressed in tumor tissues by IHC with a mutation frequency of about 4%. CUL7 is an independent prognostic factor for colorectal cancer. The nomogram constructed has effective predictive performance, and external databases proved the prognostic value of CUL7. In addition, PPI network analysis showed that CUL7 was closely related to FBXW8, and further pathway enrichment analysis showed that CUL7 was mainly involved in ubiquitin-mediated proteolysis. Therefore, our study provides a comprehensive understanding of the potential role of CUL7 in different tumors, and CUL7 might be a prognostic marker for COAD. [ABSTRACT FROM AUTHOR]

Background: ZEB2 is a protein-coding gene that is differentially expressed in tumors and can regulate the growth of tumor cells. This study investigated the specific regulatory mechanism of ZEB2 in COAD, a common cancer with high rates of morbidity and mortality. Methods: Multi-omics panoramic display of expression and function of ZEB2 in colon cancer. R software was used to study the expression of ZEB2 in 33 types of cancer. Furthermore, RT-PCR was used to detect the expression of ZEB2 in colon cancers and para-cancer tissues, as well as in colon cancer cells and normal cells. The ssGSEA was then used to explore the relationship between ZEB2 and immune cells, with UALCAN, EWAS and MEXPRESS applied to explore the methylation of ZEB2. The relationship between immunomodulators and chemokines (or receptors) based on expression data, copy number data, methylation data, and mutation data of ZEB2 was investigated using TISIDB. Finally, a protein interaction network of ZEB2 was constructed, and GO and KEGG analyses were performed on the differentially expressed genes. Results: ZEB2 is downregulated in most cancers, including COAD. The infiltration of the immune cells NK CD56 and Th17 cells was negatively correlated with ZEB2 expression, while the other 22 cells were positively correlated with ZEB2 expression. The DNA methylation of ZEB2 and the methylation of the ZEB2 protein on the EWAS website increased significantly. Analysis of the methylation levels and ZEB2 expression revealed that only the DNA methylation level and the expression of ZEB2 were significantly negatively correlated. The tumor-infiltrating lymphocytes positively correlated with the expression of ZEB2 but negatively correlated with the methylation of ZEB2. The same trend was observed for immunomodulators, chemokines, and receptors. The network showed that the protein performed certain biological functions, thereby affecting disease symptoms. Conclusion: These findings provide evidence that ZEB2-based therapy may represent a powerful treatment strategy for COAD. [ABSTRACT FROM AUTHOR]

Background: Pyroptosis has been demonstrated to be an inflammatory form of programmed cell death recently. However, the expression of pyroptosis-related genes (PRGs) in colon adenocarcinoma (COAD) and their correlationswith prognosis remain unclear. Methods: Data of COAD patients were obtained from The Cancer Genome Atlas (TCGA) database to screen differentially expressed genes (DEGs). Univariate Cox regression analysis and the LASSO Cox regression analysis were applied to construct a gene signature. All COAD patients in TCGA cohort were separated into low-risk subgroup or high-risk subgroup via the risk score. Kaplan-Meier survival analysis and receiver operator characteristic (ROC) curves were adopted to assess its prognostic efficiency. COAD data from the GSE17537 datasets was used for validation. A prognostic nomogram was established to predict individual survival. The correlation between PRGs and immune cell infiltration in COAD was verified based on TIMER database. CIBERSORT analysis was utilized on risk subgroup as defined by model. The protein and mRNA expression level of PRGs were verified by HPA database and qPCR. Results: A total of 51 differentially expressed PRGs were identified in TCGA cohort. Through univariate Cox regression analysis and LASSO Cox regression analysis, a prognostic model containing 7 PRGs was constructed. Kaplan-Meier survival analysis indicated that patients in the low-risk subgroup exhibited better prognosis compared to those in the high-risk subgroup. Additionally, the area under the curve (AUC) of ROC is 0.60, 0.63, and 0.73 for 1-, 3-, and 5-year survival in TCGA cohort and 0.63, 0.65, and 0.64 in validation set. TIMER database showed a strong correlation between 7 PRGs and tumor microenvironment in COAD. Moreover, CIBERSORT showed significant differences in the infiltration of plasma cells, M0 macrophages, resting dendritic cells, and eosinophils between low-risk subgroup and high-risk subgroup. HPA database showed that protein expression level of SDHB, GZMA, BTK, EEF2K, and NR1H2 was higher in normal tissues. And the transcriptional level of CASP5, BTK, SDHB, GZMA, and RIPK3 was high in normal tissues. Conclusions: Our study identified a novel PRGs signature that could be used to predict the prognosis of COAD patients, which might provide a new therapeutic target for the treatment of COAD patients. [ABSTRACT FROM AUTHOR]

Spindle pole body component 25(SPC25) is involved in a variety of biological processes, including carcinogenesis. However, no research has been done on the clinical importance of SPC25 in colorectal adenocarcinoma (COAD). The goal of this work was to investigate the mRNA level of SPC25 in COAD and normal tissues, as well as its diagnostic and prognostic usefulness. The mRNA level of SPC25 was examined in colorectal adenocarcinoma (COAD) using Gene Expression Profiling Interactive Analysis (GEPIA), Firebrowse, Gene Expression Omnibus (GEO), Oncomine and The Cancer Genome Atlas (TCGA) databases. To examine the diagnostic significance of SPC25, we use receiver operating characteristic (ROC) plotter. SPC25 was upregulated in several type of cancers, and the highest expression was in COAD cohort study. SPC25 was higher in tumor COAD tissues in comparison to normal tissues (p value <0.001). High level of SPC25 at mRNA level was associated with tumor stage (p value= 0.045) and lymph node (p value= 0.019). Patients with high SPC25 had poor overall survival and disease free survival. In ROC analysis, SPC25 was shown to be a highly diagnostic biomarker in COAD with Area value =0.548 and p value= 4.5e-2. SPC25 was elevated in COAD and was found to be an independent predictor of worse Overall Survival and Disease free survival in patients with COAD. Therefore, SPC25 is a useful biomarker for diagnostic and prognostic COAD patients. [ABSTRACT FROM AUTHOR]

Abstract Background Traditionally, mutational burden and mutational signatures have been assessed by tumor-normal pair DNA sequencing. The requirement of having both normal and tumor samples is not always feasible from a clinical perspective, and led us to investigate the efficacy of using RNA sequencing of only the tumor sample to determine the mutational burden and signatures, and subsequently molecular cause of the cancer. The potential advantages include reducing the cost of testing, and simultaneously providing information on the gene expression profile and gene fusions present in the tumor. Results In this study, we devised supervised and unsupervised learning methods to determine mutational signatures from tumor RNA-seq data. As applications, we applied the methods to a training set of 587 TCGA uterine cancer RNA-seq samples, and examined in an independent testing set of 521 TCGA colorectal cancer RNA-seq samples. Both diseases are known associated with microsatellite instable high (MSI-H) and driver defects in DNA polymerase ɛ (POLɛ). From RNA-seq called variants, we found majority (> 95%) are likely germline variants, leading to C > T enriched germline variants (dbSNP) widely applicable in tumor and normal RNA-seq samples. We found significant associations between RNA-derived mutational burdens and MSI/POLɛ status, and insignificant relationship between RNA-seq total coverage and derived mutational burdens. Additionally we found that over 80% of variants could be explained by using the COSMIC mutational signature-5, -6 and -10, which are implicated in natural aging, MSI-H, and POLɛ, respectively. For classifying tumor type, within UCEC we achieved a recall of 0.56 and 0.78, and specificity of 0.66 and 0.99 for MSI and POLɛ respectively. By applying learnt RNA signatures from UCEC to COAD, we were able to improve our classification of both MSI and POLɛ. Conclusions Taken together, our work provides a novel method to detect RNA-seq derived mutational signatures with effective procedures to remove likely germline variants. It can leads to accurate classification of underlying driving mechanisms of DNA damage deficiency.

Colon adenocarcinoma (COAD) represents a frequent malignant tumor of the digestive system with high mortality and poor prognosis. As a prevalent internal mRNA modification in eukaryotic cells, N6-methyladenosine (m6A) has been reported to participate in tumor malignancy. This study is designed to explore the role and mechanism of Methyltransferase-like 3 (METTL3) in the progression of COAD. In this research, the GEPIA database was applied to analyze the relationship between COAD and cell division cycle-associated protein 7 (CDCA7) or METTL3. Cell viability, cell cycle progression, apoptosis, migration, and invasion were detected by Cell Counting Kit-8 (CCK-8), flow cytometry, transwell assays. The glycolysis level was detected via specific kits. CDCA7, E-cadherin, N-cadherin, and METTL3 protein levels were determined by western blot assay. The biological role of CDCA7 on COAD tumor growth was examined by the xenograft tumor model in vivo. After RBPsuite analysis, the interaction between METTL3 and CDCA7 was verified by methylated RNA immunoprecipitation (MeRIP). METTL3 and CDCA7 were highly expressed in COAD tissues and cells. Furthermore, the silencing of CDCA7 hindered COAD cell proliferation, migration, invasion, glycolysis, EMT, and promoted apoptosis in vitro , as well as retarded tumor growth in vivo. At the molecular level, METTL3 might enhance the stability of CDCA7 mRNA via m6A methylation. METTL3 contributes to the malignant progression of COAD cells partly by regulating the stability of CDCA7 mRNA, providing a promising therapeutic target for COAD treatment. [ABSTRACT FROM AUTHOR]

Patients with colonic adenocarcinoma (COAD) are at relatively high risk of SARS-CoV-2 infection. However, there is a lack of medical strategies to treat COVID-19/COAD comorbidity. Puerarin, a natural product, is a known antiviral, antitumor, and immunomodulatory effect. Therefore, we hypothesised that puerarin could be used to treat COVID-19/COAD patients. Based on network pharmacology and bioinformatics analysis, the potential targets and pharmacological mechanisms of puerarin in COVID-19/COAD were identified. By intersecting therapeutic target genes for puerarin, COVID-19-related genes and COAD-related genes, 42 target genes of puerarin that could potentially treat COVID-19/COAD comorbidity were obtained. By using the 42 potential target genes to construct the protein-protein interaction (PPI) network, we obtained five core target genes, namely RELA, BCL2, JUN, FOS, and MAPK1. The results of bioinformatics analysis revealed that puerarin could be able to treat COVID-19/COAD comorbidity through apoptosis, antiviral, antioxidant, NF-κB signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, TNF signaling pathway, and HIF-1 signaling pathway etc. This study found that puerarin has the potential to treat COVID-19/COAD patients and that the therapeutic target genes obtained in the study may provide clues for the treatment of COVID19/COAD comorbidity. [ABSTRACT FROM AUTHOR]

Treatment resistance is observed in all advanced cancers. Colorectal cancer (CRC) presenting as colorectal adenocarcinoma (COAD) is the second leading cause of cancer deaths worldwide. Multimodality treatment includes surgery, chemotherapy, and targeted therapies with selective utilization of immunotherapy and radiation therapy. Despite the early success of anti-epidermal growth factor receptor (anti-EGFR) therapy, treatment resistance is common and often driven by mutations in APC, KRAS, RAF, and PI3K/mTOR and positive feedback between activated KRAS and WNT effectors. Challenges in the direct targeting of WNT regulators and KRAS have caused alternative actionable targets to gain recent attention. Utilizing an unbiased drug screen, we identified combinatorial targeting of DDR1/BCR-ABL signaling axis with small-molecule inhibitors of EGFR-ERBB2 to be potentially cytotoxic against multicellular spheroids obtained from WNT-activated and KRAS-mutant COAD lines (HCT116, DLD1, and SW480) independent of their KRAS mutation type. Based on the data-driven approach using available patient datasets (The Cancer Genome Atlas (TCGA)), we constructed transcriptomic correlations between gene DDR1, with an expression of genes for EGFR, ERBB2-4, mitogen-activated protein kinase (MAPK) pathway intermediates, BCR, and ABL and genes for cancer stem cell reactivation, cell polarity, and adhesion; we identified a positive association of DDR1 with EGFR, ERBB2, BRAF, SOX9, and VANGL2 in Pan-Cancer. The evaluation of the pathway network using the STRING database and Pathway Commons database revealed DDR1 protein to relay its signaling via adaptor proteins (SHC1, GRB2, and SOS1) and BCR axis to contribute to the KRAS-PI3K-AKT signaling cascade, which was confirmed by Western blotting. We further confirmed the cytotoxic potential of our lead combination involving EGFR/ERBB2 inhibitor (lapatinib) with DDR1/BCR-ABL inhibitor (nilotinib) in radioresistant spheroids of HCT116 (COAD) and, in an additional devastating primary cancer model, glioblastoma (GBM). GBMs overexpress DDR1 and share some common genomic features with COAD like EGFR amplification and WNT activation. Moreover, genetic alterations in genes like NF1 make GBMs have an intrinsically high KRAS activity. We show the combination of nilotinib plus lapatinib to exhibit more potent cytotoxic efficacy than either of the drugs administered alone in tumoroids of patient-derived recurrent GBMs. Collectively, our findings suggest that combinatorial targeting of DDR1/BCR-ABL with EGFR-ERBB2 signaling may offer a therapeutic strategy against stem-like KRAS-driven chemoradioresistant tumors of COAD and GBM, widening the window for its applications in mainstream cancer therapeutics. [ABSTRACT FROM AUTHOR]

Colon adenocarcinoma (COAD) is one of the most common malignancies, and its metastatic lesions are the leading cause of death in COAD patients. PANoptosis is a recently identified pathway for programmed cell death implicated in developing COAD. Long non-coding RNAs (lncRNAs) are key regulators of cancer occurrence and progress. Although their function has captured much attention in COAD, the relationship between COAD metastasis-associated lncRNA expression and PANoptosis remains elusive. Therefore, this study aimed to explore the potential regulatory roles of metastasis- and PANoptosis-associated lncRNAs in COAD. Nine lncRNAs associated with metastasis and PANoptosis in COAD were identified from The Cancer Genome Atlas (TCGA) and GEO databases. Their functions were analyzed by multiple bioinformatics methods, and the lncRNA-miRNA-mRNA network was constructed. Multivariate Cox analysis identified one lncRNA (SNHG7) significantly related to COAD prognosis. Subsequent analyses showed its expression correlated with tumor stage and lymph node metastasis. Moreover, drug sensitivity analysis and in vitro experiments suggest that lncRNA SNHG7 contributes to drug resistance in COAD. In summary, lncRNA SNHG7 is a potential target for diagnosing and treating COAD and plays a crucial role in regulating apoptosis, metastasis, and drug resistance in COAD. [ABSTRACT FROM AUTHOR]

Background: MICAL-like protein 2 (MICAL-L2), a member of the molecules interacting with CasL (MICAL) family of proteins, is strongly associated with the malignancy of multiple types of cancer. However, the role of MICAL-L2 in colon adenocarcinoma (COAD) has not been well characterized.Methods: In this study, we analyzed the role of MICAL-L2 in COAD using datasets available from public databases. The mRNA and protein expression of MICAL-L2 was investigated using TCGA, UALCAN, and independent immunohistochemical assays. Overall survival (OS) and disease-specific survival (DSS) of COAD patients were assessed based on the MICAL-L2 expression level using the Kaplan-Meier method. Univariate and multivariate analysis was employed to determine whether MICAL-L2 could serve as an independent prognostic indicator of OS. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were further utilized to explore the possible cellular mechanism underlying the role of MICAL-L2 in COAD. In addition, the correlation between MICAL-L2 expression and immune cell infiltration levels was investigated via single-sample gene set enrichment analysis (ssGSEA).Results: Data from TCGA, HPA, and UALCAN datasets indicated that MICAL-L2 expression was significantly higher in COAD tissue than in adjacent normal tissues, and this was confirmed by immunohistochemical assays. Kaplan-Meier survival analysis revealed that patients with MICAL-L2 had shorter OS and DSS. Furthermore, multivariate Cox analysis indicated that MICAL-L2 was an independent risk factor for OS in COAD patients. ROC analysis confirmed the diagnostic value of MICAL-L2, and a prognostic nomogram involving age, M stage, and MICAL-L2 expression was constructed for OS. Functional enrichment analyses revealed that transport-related activity was closely associated with the role of MICAL-L2 in COAD. Regarding immune infiltration levels, MICAL-L2 was found to be positively associated with CD56bright NK cells.Conclusions: Our results suggested that MICAL-L2 is a promising biomarker for determining prognosis and correlated with immune infiltration levels in COAD. [ABSTRACT FROM AUTHOR]

Background: Colon adenocarcinoma (COAD) is one of the common cancers worldwide. Collagen triple helix repeat containing 1 (CTHRC1) has been reported to be involved in cell invasion, angiogenesis, and the promotion of epithelial-mesenchymal transformation by mediating multiple signaling pathways. However, the role of CTHRC1 in COAD has not yet been determined. Methods: Differentially expressed genes were evaluated using gene expression data from the Oncomine and TIMER databases. Correlations between CTHRC1 gene expression and clinicopathological factors were analyzed using gene expression data from UALCAN databases. Then, we searched the GEPIA database to evaluate the association of CTHRC1 gene expression with clinical outcomes. The cBioPortal database was used to analyze CTHRC1 genetic alterations. Subsequently, the TIMER website was chosen to assess the correlation of CTHRC1 with the tumor immune cell infiltration level. The TCGA dataset was used for a gene set enrichment analysis (GSEA). Result: CTHRC1 was highly expressed in COAD patients, and significantly related to poor prognosis. In addition, elevated expression of CTHRC1 was related to the clinical stage and pathological type of COAD. The GSEA analysis showed that CTHRC1 was enriched in Gα signaling, GCPR ligand binding, neutrophil degranulation, interleukin signaling, and tumor-associated pathways. In addition, CTHRC1 was significantly associated with the expression of multiple immune markers related to specific immune cells. Conclusion: This study suggest that CTHRC1 expression is related to the prognosis and immune infiltration of COAD patients. Therefore, CTHRC1 may be a new candidate prognostic biomarker for determining immune infiltration levels and providing COAD prognoses. [ABSTRACT FROM AUTHOR]

Colon adenocarcinoma (COAD) is one of the most common malignancies, and its metastatic lesions are the leading cause of death in COAD patients. PANoptosis is a recently identified pathway for programmed cell death implicated in developing COAD. Long non-coding RNAs (lncRNAs) are key regulators of cancer occurrence and progress. Although their function has captured much attention in COAD, the relationship between COAD metastasis-associated lncRNA expression and PANoptosis remains elusive. Therefore, this study aimed to explore the potential regulatory roles of metastasis- and PANoptosis-associated lncRNAs in COAD. Nine lncRNAs associated with metastasis and PANoptosis in COAD were identified from The Cancer Genome Atlas (TCGA) and GEO databases. Their functions were analyzed by multiple bioinformatics methods, and the lncRNA-miRNA-mRNA network was constructed. Multivariate Cox analysis identified one lncRNA (SNHG7) significantly related to COAD prognosis. Subsequent analyses showed its expression correlated with tumor stage and lymph node metastasis. Moreover, drug sensitivity analysis and in vitro experiments suggest that lncRNA SNHG7 contributes to drug resistance in COAD. In summary, lncRNA SNHG7 is a potential target for diagnosing and treating COAD and plays a crucial role in regulating apoptosis, metastasis, and drug resistance in COAD.

Treatment resistance is observed in all advanced cancers. Colorectal cancer (CRC) presenting as colorectal adenocarcinoma (COAD) is the second leading cause of cancer deaths worldwide. Multimodality treatment includes surgery, chemotherapy, and targeted therapies with selective utilization of immunotherapy and radiation therapy. Despite the early success of anti-epidermal growth factor receptor (anti-EGFR) therapy, treatment resistance is common and often driven by mutations in APC, KRAS, RAF, and PI3K/mTOR and positive feedback between activated KRAS and WNT effectors. Challenges in the direct targeting of WNT regulators and KRAS have caused alternative actionable targets to gain recent attention. Utilizing an unbiased drug screen, we identified combinatorial targeting of DDR1/BCR-ABL signaling axis with small-molecule inhibitors of EGFR-ERBB2 to be potentially cytotoxic against multicellular spheroids obtained from WNT-activated and KRAS-mutant COAD lines (HCT116, DLD1, and SW480) independent of their KRAS mutation type. Based on the data-driven approach using available patient datasets (The Cancer Genome Atlas (TCGA)), we constructed transcriptomic correlations between gene DDR1, with an expression of genes for EGFR, ERBB2-4, mitogen-activated protein kinase (MAPK) pathway intermediates, BCR, and ABL and genes for cancer stem cell reactivation, cell polarity, and adhesion; we identified a positive association of DDR1 with EGFR, ERBB2, BRAF, SOX9, and VANGL2 in Pan-Cancer. The evaluation of the pathway network using the STRING database and Pathway Commons database revealed DDR1 protein to relay its signaling via adaptor proteins (SHC1, GRB2, and SOS1) and BCR axis to contribute to the KRAS-PI3K-AKT signaling cascade, which was confirmed by Western blotting. We further confirmed the cytotoxic potential of our lead combination involving EGFR/ERBB2 inhibitor (lapatinib) with DDR1/BCR-ABL inhibitor (nilotinib) in radioresistant spheroids of HCT116 (COAD) and, in an additional devastating primary cancer model, glioblastoma (GBM). GBMs overexpress DDR1 and share some common genomic features with COAD like EGFR amplification and WNT activation. Moreover, genetic alterations in genes like NF1 make GBMs have an intrinsically high KRAS activity. We show the combination of nilotinib plus lapatinib to exhibit more potent cytotoxic efficacy than either of the drugs administered alone in tumoroids of patient-derived recurrent GBMs. Collectively, our findings suggest that combinatorial targeting of DDR1/BCR-ABL with EGFR-ERBB2 signaling may offer a therapeutic strategy against stem-like KRAS-driven chemoradioresistant tumors of COAD and GBM, widening the window for its applications in mainstream cancer therapeutics.

Patients with colonic adenocarcinoma (COAD) are at relatively high risk of SARS-CoV-2 infection. However, there is a lack of medical strategies to treat COVID-19/COAD comorbidity. Puerarin, a natural product, is a known antiviral, antitumor, and immunomodulatory effect. Therefore, we hypothesised that puerarin could be used to treat COVID-19/COAD patients. Based on network pharmacology and bioinformatics analysis, the potential targets and pharmacological mechanisms of puerarin in COVID-19/COAD were identified. By intersecting therapeutic target genes for puerarin, COVID-19-related genes and COAD-related genes, 42 target genes of puerarin that could potentially treat COVID-19/COAD comorbidity were obtained. By using the 42 potential target genes to construct the protein-protein interaction (PPI) network, we obtained five core target genes, namely RELA, BCL2, JUN, FOS, and MAPK1. The results of bioinformatics analysis revealed that puerarin could be able to treat COVID-19/COAD comorbidity through apoptosis, antiviral, antioxidant, NF-κB signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, TNF signaling pathway, and HIF-1 signaling pathway etc. This study found that puerarin has the potential to treat COVID-19/COAD patients and that the therapeutic target genes obtained in the study may provide clues for the treatment of COVID19/COAD comorbidity.

Background: Ferroptosis induced by SLC7A11 has an important translational value in the treatment of cancers. However, the mechanism of SLC7A11 in the pathogenesis of colon adenocarcinoma (COAD) is rarely studied in detail.Methods: SLC7A11 expression was explored with The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) databases, and Western blot assay. The correlation of SLC7A11 expression with the abundance of infiltrating immune cells was evaluated via the TIMER database. The relation of SLC7A11 expression with immune cell markers was investigated via Gene Expression Profiling Interactive Analysis (GEPIA). The co-expression genes of SLC7A11 were screened by R packages, and the PPI was constructed via the STRING database. SLC7A11 and co-expressed gene modulators were selected by NetworkAnalyst and DSigDB database. The correlations between SLC7A11 and cancer immune characteristics were analyzed via the TIMER and TISIDB databases.Results: SLC7A11 is overexpressed in most tumors, including COAD. The expression level of SLC7A11 has a significant correlation with the infiltration levels of CD8+ T cells, neutrophils, and dendritic cells in COAD. The infiltrated lymphocyte markers of Th1 cell such as TBX21, IL12RB2, IL27RA, STAT1, and IFN-γ were strongly correlated with SLC7A11 expression. Five hub genes co-expressed with SLC7A11 that induce ferroptosis were identified, and mir-335-5p, RELA, and securinine have regulatory effects on it. SLC7A11 was negatively correlated with the expression of chemokines and chemokine receptors, such as CCL17, CCL19, CCL22, CCL23, CXCL14, CCR10, CX3CR1, and CXCR3, in COAD.Conclusion: SLC7A11 may play a role in induced ferroptosis and regulating tumor immunity, which can be considered as potential therapeutic targets in COAD.

BackgroundColon adenocarcinoma (COAD) is a highly heterogeneous disease, thus making prognostic predictions uniquely challenging. Metabolic reprogramming is emerging as a novel cancer hallmark that may serve as the basis for more effective prognosis strategies.MethodsThe mRNA expression profiles and relevant clinical information of COAD patients were downloaded from public resources. The least absolute shrinkage and selection operator (LASSO) Cox regression model was exploited to establish a prognostic model, which was performed to gain risk scores for multiple genes in The Cancer Genome Atlas (TCGA) COAD patients and validated in GSE39582 cohort. A forest plot and nomogram were constructed to visualize the data. The clinical nomogram was calibrated using a calibration curve coupled with decision curve analysis (DCA). The association between the model genes' expression and six types of infiltrating immunocytes was evaluated. Apoptosis, cell cycle assays and cell transfection experiments were performed.ResultsUnivariate Cox regression analysis results indicated that ten differentially expressed genes (DEGs) were related with disease-free survival (DFS) (P-value< 0.01). A four-gene signature was developed to classify patients into high- and low-risk groups. And patients with high-risk exhibited obviously lower DFS in the training and validation cohorts (P < 0.05). The risk score was an independent parameter of the multivariate Cox regression analyses of DFS in the training cohort (HR > 1, P-value< 0.001). The same findings for overall survival (OS) were obtained GO enrichment analysis revealed several metabolic pathways with significant DEGs enrichment, G1/S transition of mitotic cell cycle, CD8+ T-cells and B-cells may be significantly associated with COAD in DFS and OS. These findings demonstrate that si-FUT1 inhibited cell migration and facilitated apoptosis in COAD.ConclusionThis research reveals that a novel metabolic gene signature could be used to evaluate the prognosis of COAD, and targeting metabolic pathways may serve as a therapeutic alternative.

Background: Colon adenocarcinoma (COAD) is still the main cause of cancer deaths worldwide. Although immunotherapy has made progress in recent years, there is still a need to improve diagnosis, prognosis, and treatment tools. UL-16 binding protein 1 (ULBP1) is a ligand that activates the receptor natural killer cell group 2 receptor D (NKG2D) and plays an important immunomodulatory role. We aimed to investigate the clinical significance of ULBP1 in COAD. Methods: We obtained the relevant data from The Cancer Genome Atlas (TCGA). A total of 438 patients with COAD were included in this study, with a mean age of 67.1 ± 13.03 years old, of which 234 (53.42%) were male. The diagnostic value of COAD tumor tissues and adjacent tissues was analyzed by ROC curve. Univariate and multivariate survival analysis investigated the prognostic value of ULBP1 gene, and Gene Set Enrichment Analysis (GSEA) curve was performed to analyze the biological process and enriched enrichment pathway of ULBP1 in COAD. Combination survival analysis investigated the combined prognostic effect of prognostic genes. Results: ULBP1 gene had a high diagnostic value in COAD [AUC (TCGA) = 0.959; AUC (Guangxi) = 0.898]. Up-regulated ULBP1 gene of patients with COAD predicted a worse prognosis compared to those patients with down-regulated ULBP1 gene (Adjusted HR = 1.544, 95% CI = 1.020–2.337, p = 0.040). The GSEA showed that ULBP1 was involved in the apoptotic pathway and biological process of T cell mediated cytotoxicity, regulation of natural killer cell activation, and T cell mediated immunity of COAD. The combination survival analysis showed that the combination of high expression of ULBP1 , AARS1 , and DDIT3 would increase the 2.2-fold death risk of COAD when compared with those of low expression genes. Conclusion: The immune-related ULBP1 gene had diagnostic and prognostic value in COAD. The combination of ULBP1 , AARS1 , and DDIT3 genes could improve the prognostic prediction performance in COAD. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) and their N6-methyladenosine (m6A) modifications play an essential role in tumorigenesis and cancer progression. This study was designed to explore the value of m6A-related lncRNAs in prognosis and therapeutic applications of immune infiltration of colon adenocarcinoma (COAD). We downloaded the COAD gene expression and clinical data from The Cancer Genome Atlas project. By co-expression analysis, Lasso Cox regression analysis, and univariate and multivariate Cox regression, we constructed an independent prognostic signature of seven m6A-related lncRNAs. The prognostic lncRNAs were divided into two clusters by consistent clustering analysis, as well as into two groups of low–high risk based on the signature. Then we identified the relationship between the different groups with clinical features and immune cell infiltration. Cluster 2 had a higher risk score with a lower survival rate. The risk score was higher in groups with advanced clinical features, such as stage III–IV, N1-3, and M1. The expression of AC156455.1 was increased in tumor tissues and cluster 2, and the lncRNA ZEB1−AS1 was notably higher in the high-risk group. Five types of immune cells showed differences in two clusters, and most were upregulated in type 2. The expression of memory B cells was positively correlated with the risk score. The prognostic model was verified by the Gene Expression Omnibus (GEO) dataset. Besides, we found that the expression of these seven lncRNAs in tumor tissues was significantly higher than that in normal tissues, which verified the feasibility of the model. Thus, the signature of seven m6A-related lncRNAs can independently predict the prognosis of COAD. This signature is also closely associated with immune cell infiltration, and new therapeutic targets can be explored from this field. [ABSTRACT FROM AUTHOR]

Abstract Aim This scoping review will gather existing evidence on specific interventions at presentation and discharge which aim to standardize care and/or reduce unnecessary admissions and/or readmissions to hospital for patients presenting with acute exacerbation of chronic obstructive pulmonary (airways) disease. Design Scoping review of relevant literature from January 2000–March 2019. Methods Database searches for primary evidence in peer‐reviewed journals will be conducted electronically using Web of Science, EMBASE (Elsevier) and PUBMED. Eligibility criteria will include hospital‐based interventions for presentations of acute exacerbation of chronic obstructive pulmonary disease with outcomes specific to standardizing care or reducing unnecessary admissions or readmissions. Abstract, full‐text screening and data extraction will be completed independently by a panel of expert reviewers. Results We aim to identify current interventions and improvement approaches in acute exacerbation of chronic obstructive pulmonary (airways) disease care that have an impact on admission and discharge processes or readmissions. Recommendations as a result of this review will aid the design and development of future improvement intervention.

Background: Colon adenocarcinoma (COAD) is still the main cause of cancer deaths worldwide. Although immunotherapy has made progress in recent years, there is still a need to improve diagnosis, prognosis, and treatment tools. UL-16 binding protein 1 (ULBP1) is a ligand that activates the receptor natural killer cell group 2 receptor D (NKG2D) and plays an important immunomodulatory role. We aimed to investigate the clinical significance of ULBP1 in COAD.Methods: We obtained the relevant data from The Cancer Genome Atlas (TCGA). A total of 438 patients with COAD were included in this study, with a mean age of 67.1 ± 13.03 years old, of which 234 (53.42%) were male. The diagnostic value of COAD tumor tissues and adjacent tissues was analyzed by ROC curve. Univariate and multivariate survival analysis investigated the prognostic value of ULBP1 gene, and Gene Set Enrichment Analysis (GSEA) curve was performed to analyze the biological process and enriched enrichment pathway of ULBP1 in COAD. Combination survival analysis investigated the combined prognostic effect of prognostic genes.Results:ULBP1 gene had a high diagnostic value in COAD [AUC (TCGA) = 0.959; AUC (Guangxi) = 0.898]. Up-regulated ULBP1 gene of patients with COAD predicted a worse prognosis compared to those patients with down-regulated ULBP1 gene (Adjusted HR = 1.544, 95% CI = 1.020–2.337, p = 0.040). The GSEA showed that ULBP1 was involved in the apoptotic pathway and biological process of T cell mediated cytotoxicity, regulation of natural killer cell activation, and T cell mediated immunity of COAD. The combination survival analysis showed that the combination of high expression of ULBP1, AARS1, and DDIT3 would increase the 2.2-fold death risk of COAD when compared with those of low expression genes.Conclusion: The immune-related ULBP1 gene had diagnostic and prognostic value in COAD. The combination of ULBP1, AARS1, and DDIT3 genes could improve the prognostic prediction performance in COAD.

Background: Colon cancer (COAD) has been identified as being among the most prevalent tumors globally and ranked the third major contributor to cancer-related mortality. COAD is a molecularly heterogeneous disease. There are great differences in clinical manifestations and prognosis among different molecular subtypes.Methods:379 TCGA-COAD samples were divided into four subtypes: primary proliferative, with collective, crypt-like, and EMT invasion. The differences among the four subtypes were analyzed from the multidimensional perspectives of immunity, genomic variation, and prognosis. The limma package was utilized to identify differentially expressed genes (DEGs) amongst different molecular subtypes. Phenotype-related coexpressed gene modules were identified using WGCNA. The polygenic prognosis model was created utilizing the lasso Cox analysis and verified by time-dependent subject operating characteristics (ROC).Results: There are some differences in prognosis, TMB and common gene variation, immune score, and immunotherapy/chemotherapy between proliferative and three invasive molecular subtypes. 846 differential genes (DEGs) were obtained by limma packet analysis. Differential gene analysis was utilized to screen the DEGs among distinct subtypes, which were significantly enriched in the pathways related to tumorigenesis and development. Co-expression network analysis found 46 co-expressed genes correlated with proliferative and three invasive phenotypes. Based on differentially co-expressed genes, we developed a prognostic risk model of 8-genes signature, which exhibited strong stability regardless of external and internal validation. RT-PCR experiments proved the expression of eight genes in tumor and normal samples.Conclusion: We have developed an eight-gene signature prognostic stratification system. Furthermore, we proposed that this classifier can serve as a molecular diagnostic tool to assess the prognosis of colon cancer patients.

Background: Colon adenocarcinoma (COAD) is one of the most prevalent cancers worldwide and has become a leading cause of cancer death. Although many potential biomarkers of COAD have been screened with the bioinformatics method, it is necessary to explore novel markers for the diagnosis and appropriate individual treatments for COAD patients due to the high heterogeneity of this disease. Epithelial-to-mesenchymal transition (EMT)-mediated tumor metastasis suggests poor prognosis of cancers. Ferroptosis is involved in tumor development. EMT signaling can increase the cellular sensitivity to ferroptosis in tumors. The aim of our study is finding novel prognostic biomarkers to determine COAD patients for predicting efficiency of metastasis status and targeting precise ferroptosis-related therapy.Methods: A novel gene signature related to metastasis and ferroptosis was identified combing with risk model and WGCNA analysis with R software. The biological functions and predictive ability of the signature in COAD were explored through bioinformatics analysis.Results: We established a four-gene prognostic signature (MMP7, YAP1, PCOLCE, and HOXC11) based on EMT and ferroptosis related genes and validated the reliability and effectiveness of this model in COAD. This four-gene prognostic signature was closely connected with metastasis and ferroptosis sensitivity of COAD. Moreover, WGCNA analysis further confirmed the correlation between PCOLCE, HOXC11, and liver and lymphatic invasion of COAD.Conclusion: The four genes may become potential prognostic biomarkers to identify COAD patients with metastasis. Moreover, this four-gene signature may be able to determine the COAD suitable with ferroptosis induction therapy. Finally, PCOLCE2 and HOXC11 were selected individually because of their novelties and precise prediction ability. Overall, this signature provided novel possibilities for better prognostic evaluation of COAD patients and may be of great guiding significance for individualized treatment and clinical decision.

Long non-coding RNAs (lncRNAs) and their N6-methyladenosine (m6A) modifications play an essential role in tumorigenesis and cancer progression. This study was designed to explore the value of m6A-related lncRNAs in prognosis and therapeutic applications of immune infiltration of colon adenocarcinoma (COAD). We downloaded the COAD gene expression and clinical data from The Cancer Genome Atlas project. By co-expression analysis, Lasso Cox regression analysis, and univariate and multivariate Cox regression, we constructed an independent prognostic signature of seven m6A-related lncRNAs. The prognostic lncRNAs were divided into two clusters by consistent clustering analysis, as well as into two groups of low–high risk based on the signature. Then we identified the relationship between the different groups with clinical features and immune cell infiltration. Cluster 2 had a higher risk score with a lower survival rate. The risk score was higher in groups with advanced clinical features, such as stage III–IV, N1-3, and M1. The expression of AC156455.1 was increased in tumor tissues and cluster 2, and the lncRNA ZEB1−AS1 was notably higher in the high-risk group. Five types of immune cells showed differences in two clusters, and most were upregulated in type 2. The expression of memory B cells was positively correlated with the risk score. The prognostic model was verified by the Gene Expression Omnibus (GEO) dataset. Besides, we found that the expression of these seven lncRNAs in tumor tissues was significantly higher than that in normal tissues, which verified the feasibility of the model. Thus, the signature of seven m6A-related lncRNAs can independently predict the prognosis of COAD. This signature is also closely associated with immune cell infiltration, and new therapeutic targets can be explored from this field.

Background: Embryonic stem cell-related gene (ESRG; also known as HESRG) is a long non-coding RNA (lncRNA). It is involved in the regulation of human pluripotent stem cells (hPSCs) self-renewal. ESRG gene has the ability to interact with chromatins, different RNA types, and RNA binding proteins (RBP); thus making ESRG be considered an oncogenic lncRNA, where its expression is detected in various tumor tissues. This study aimed to evaluate the prospective diagnostic and prognostic values of ESRG in various human cancers., Materials and Methods: The expression of ESRG in various cancers was analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA), Tumor Immune Estimation Resource (TIMER), and University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN) databases. Moreover, the correlation between the expression of ESRG and clinical pathological parameters was analyzed using UALCAN. The effect of ESRG expression on the survival outcome was evaluated using Kaplan-Meier plotter, UALCAN, GEPIA, and TIMER. The correlation between ESRG expression and immune cell infiltration was studied by TIMER. Additionally, the genetic alterations were investigated cBioportal. Our findings were validated using the GEO2R database., Results: Our results showed ESRG to be significantly up-regulated in colon adenocarcinoma (COAD) and lung squamous cell carcinoma (LUSC) with p<0.001, in addition to rectum adenocarcinoma (READ), and uterine carcinosarcoma (UCEC) with p<0.01. Regarding pathogenic stages, there was a significant upregulation in stages 2, 3, and 4 compared to normal in COAD and stages 1, 2, and 3 for LUSC patients. The combined prognostic analysis showed that the up-regulated expression of ESRG was associated with better survival outcomes in patients with brain lower-grade glioma (LGG). Our results demonstrate a significant negative correlation between ESRG expression and the abundance of CD8+T cells in COAD, READ, LUSC, and UCEC. Additionally, ESRG was mutated in 0.77 (<1%) of the queried samples, and the most prevalent ESRG mutations are deep deletion mutations, followed by amplification., Conclusion: Analysis of ESRG across various cancer types elucidated its potential to be used as a diagnostic biomarker in COAD, LUSC, READ, and UCEC and a promising prognostic biomarker in LGG. Our findings provide useful insights for future research., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Fageer et al.)

Colon adenocarcinoma (COAD) is a common malignant tumor of the digestive tract that threatens human health seriously. Thus, it is urgent to explore biomarkers that can be used to evaluate a patient's survival prognosis overall as a supplementary treatment. RNA‐seq expression profiles were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus, and Lasso and multivariate Cox regression analyses were used for developing the prognostic model. Finally, a nomogram comprising the prognostic model was established to evaluate survival overall. A risk model comprised of a total of 12 immune‐related gene pairs was constructed. Further analysis revealed the model's independent prognostic ability in relation to other clinical characteristics. This model's nomogram could help clinicians choose personalized treatment for COAD patients. This model has significant potential to complement COAD's clinical identifying characteristics, and also provide new insights into the identification of colon cancer patients with a high risk of death. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most common cancers. Almost 80% of CRC cases are colon adenocarcinomas (COADs). Several studies have indicated the role of immunotherapy in the treatment of various cancers. Our study aimed to identify immune-related long non-coding RNAs (lncRNAs) and to use them to construct a risk assessment model for evaluating COAD prognosis. Using differential expression, correlation, and Cox regression analyses, we identified three immune-related differentially expressed lncRNAs (IR-DELs) and used them to construct a risk assessment model. The area under the curve (AUC) for each receiver operating characteristic (ROC) curve at 3-, 5-, and 10-years were greater than 0.6. In addition, the risk assessment model was correlated with several immune cells and factors. The three IR-DELs (AC124067.4, LINC02604, and MIR4435-2HG) identified in this study can be used to predict outcomes for patients with COAD and might help in identifying those who can benefit from anti-tumor immunotherapy.

Colorectal cancer (CRC) is one of the most common cancers. Almost 80% of CRC cases are colon adenocarcinomas (COADs). Several studies have indicated the role of immunotherapy in the treatment of various cancers. Our study aimed to identify immune-related long non-coding RNAs (lncRNAs) and to use them to construct a risk assessment model for evaluating COAD prognosis. Using differential expression, correlation, and Cox regression analyses, we identified three immune-related differentially expressed lncRNAs (IR-DELs) and used them to construct a risk assessment model. The area under the curve (AUC) for each receiver operating characteristic (ROC) curve at 3-, 5-, and 10-years were greater than 0.6. In addition, the risk assessment model was correlated with several immune cells and factors. The three IR-DELs (AC124067.4, LINC02604, and MIR4435-2HG) identified in this study can be used to predict outcomes for patients with COAD and might help in identifying those who can benefit from anti-tumor immunotherapy. [ABSTRACT FROM AUTHOR]