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Purpose: Inflammatory markers are known to be associated with many diseases, but their role in Meige syndrome (MS) remains unclear. This study aimed to develop and validate a nomogram for the risk prediction of MS based on inflammatory markers. Patient Data and Methods: Data from 448 consecutive patients with MS at the Third People's Hospital of Henan Province between January 2022 and December 2023 were retrospectively reviewed. The MS cohort was randomly divided into separate training and validation sets. A nomogram was constructed using a multivariate logistic regression model based on data from the training set. The model's performance was validated through cross-validation, receiver operating characteristic (ROC) curve analysis, calibration curve analysis and decision curve analysis (DCA). Results: A total of five predictors, including red blood cell distribution width (RDW), hemoglobin (HGB), high-density lipoprotein cholesterol (HDL-C), the lymphocyte-to-monocyte ratio (LMR), and the systemic immune‐inflammation index (SII), were identified using multivariate logistic regression from a total of 11 variables. The cross-validation results indicated the stability of the model constructed with the above five predictors. The model showed moderate predictive ability, with an area under the ROC curve of 0.767 in the training set and 0.735 in the validation set. The calibration curve and DCA results indicate that the model has strong consistency and significant potential for clinical application. Conclusion: We constructed a nomogram based on five risk predictors, RDW, HGB, HDL-C, the LMR and the SII, to predict MS and enhance the predictive accuracy for identifying MS risk. [ABSTRACT FROM AUTHOR]

Recent studies confirmed that the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) can regulate the proliferation and migration of tumour cells.[[1], [3]] Lung adenocarcinoma (LUAD) is the subtype with the largest proportion of lung cancer.[[5]] Huang et al. confirmed that GABA content in LUAD tissues was obviously higher than normal tissues by collecting clinical tissues.[7] By analysing GABA expression in different LUAD patients, we established a GABA-driven LUAD classification and developed a GABA-driven prognostic signature. (F) Nomogram for LUAD patients. gl In conclusion, based on the differential expression of GABA in LUAD patients, we classified LUAD patients and comprehensively considered the clinical significance of the classification. After difference analysis of these genes in tumour and normal tissue by "limma" package, 108 GABA core difference genes were obtained according to the absolute value of logFC > .5 (Table S1). Based on 108 GABA core differential genes, consensus clustering was performed in The Cancer Genome Atlas (TCGA)-LUAD queue ( I n i = 555) by using the "ConsensusClusterPlus" package. [Extracted from the article]

Background: Mental stress-induced neurotransmitters can affect the immune system in various ways. Therefore, a better understanding of the role of neurotransmitters in the tumour immune microenvironment is expected to promote the development of novel anti-tumour therapies. Methods: In this study, we analysed the plasma levels of neurotransmitters in anti-programmed cell death protein 1 (PD-1) monoclonal antibody (mAb)-resistance patients and sensitive patients, to identify significantly different neurotransmitters. Subsequently, animal experiments and experiments in vitro were used to reveal the specific mechanism of norepinephrine's (NE) effect on immunotherapy. Results: The plasma NE levels were higher in anti-PD-1 mAb-resistance patients, which may be the main cause of anti-PD-1 mAb resistance. Then, from the perspective of the immunosuppressive microenvironment to explore the specific mechanism of NE-induced anti-PD-1 mAb resistance, we found that NE can affect the secretion of C-X-C Motif Chemokine Ligand 9 (CXCL9) and adenosine (ADO) in tumour cells, thereby inhibiting chemotaxis and function of CD8+ T cells. Notably, the WNT7A/β-catenin signalling pathway plays a crucial role in this progression. Conclusion: NE can affect the secretion of CXCL9 and ADO in tumour cells, thereby inhibiting chemotaxis and the function of CD8+ T cells and inducing anti-PD-1 mAb resistance in lung adenocarcinoma (LUAD). [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) have rapidly revolutionized colorectal cancer (CRC) treatment, but resistance caused by the heterogeneous tumor microenvironment (TME) still presents a challenge. Therefore, it is necessary to characterize TME immune infiltration and explore new targets to improve immunotherapy.Methods: The compositions of 64 types of infiltrating immune cells and their relationships with CRC patient clinical characteristics were assessed. Differentially expressed genes (DEGs) between "hot" and "cold" tumors were used for functional analysis. A prediction model was constructed to explore the survival of CRC patients treated with and without immunotherapy. Finally, fatty acid-binding protein (FABP6) was selected for in vitro experiments, which revealed its roles in the proliferation, apoptosis, migration, and immunogenicity of CRC tissues and cell lines.Results: The infiltration levels of several immune cells were associated with CRC tumor stage and prognosis. Different cell types showed the synergistic or antagonism infiltration patterns. Enrichment analysis of DEGs revealed that immune-related signaling was significantly activated in hot tumors, while metabolic process pathways were altered in cold tumors. In addition, the constructed model effectively predicted the survival of CRC patients treated with and without immunotherapy. FABP6 knockdown did not significantly alter tumor cell proliferation, apoptosis, and migration. FABP6 was negatively correlated with immune infiltration, and knockdown of FABP6 increased major histocompatibility complex (MHC) class 1 expression and promoted immune-related chemokine secretion, indicating the immunogenicity enhancement of tumor cells. Finally, knockdown of FABP6 could promote the recruitment of CD8+ T cells.Conclusion: Collectively, we described the landscape of immune infiltration in CRC and identified FABP6 as a potential immunotherapeutic target for treatment. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is an incurable malignancy of mature B-lymphoid cells, and its pathogenesis is only partially understood. Previous studies have demonstrated that a number of Non-Hodgkin Lymphoma (NHL) associated genes also show susceptibility to MM, suggesting malignancies originating from B cells may share similar genetic susceptibility. Several recent large-scale genome-wide association studies (GWAS) have identified HLA-I, HLA-II, CXCR5, ETS1, LPP and NCOA1 genes as genetic risk factors associated with NHL, and this study aimed to investigate whether these genes polymorphisms confer susceptibility with MM in the Chinese Han population. In 827 MM cases and 709 healthy controls of Chinese Han, seven single nucleotide polymorphisms (SNPs) in the HLA–I region (rs6457327), the HLA–II region (rs2647012 and rs7755224), the CXCR5 gene (rs4938573), the ETS1 gene (rs4937362), the LPP gene (rs6444305), and the NCOA1 region (rs79480871) were genotyped using the Sequenom platform. Our study indicated that genotype and allele frequencies of rs79480871 showed strong associations with MM patients (pa = 3.5×10−4 and pa = 1.5×10−4), and the rs6457327 genotype was more readily associated with MM patients than with controls (pa = 4.9×10−3). This study was the first to reveal the correlation between NCOA1 gene polymorphisms and MM patients, indicating that NCOA1 might be a novel susceptibility gene for MM patients in the Chinese Han population. [ABSTRACT FROM AUTHOR]

The association between polymorphisms in the nucleoside diphosphate kinase 1 ( NME1 ) gene and overall risk of cancer remains to be elucidated. Here, we performed a meta-analysis of the association between rs16949649, rs2302254, and rs34214448 polymorphisms in the NME1 gene and cancer risk. PubMed, Web of Science, and CNKI databases (as of June 6, 2017) were searched. Eight studies, encompassing 1644 cases and 2038 controls, were selected. The results revealed no significant relationship between NME1 polymorphisms and overall cancer susceptibility. Interestingly, the rs16949649 polymorphism was associated with increased susceptibility to gynecological cancer (heterozygous model: odds ratio [OR] = 1.74, 95% confidence interval [CI] = 1.06–2.86, P  = 0.029). The rs2302254 polymorphism was linked to decreased susceptibility to gastric cancer in the other groups (recessive model: OR = 0.53, 95% CI = 0.28–0.98, P  = 0.045). The rs34214448 polymorphism correlated significantly with increased susceptibility to non-small cell lung cancer according to all genetic models ( P <  0.05) and was linked to decreased risk in cervical cancer (recessive model: OR = 0.51, 95% CI = 0.27–0.94, P  = 0.031). Thus, our meta-analysis found rs16949649 associated with increased susceptibility to gynecological cancer and rs2302254 was linked to reduced gastric cancer risk; additional, larger studies are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Cervical squamous cell carcinoma (CESC) is one of the most common malignancies associated with mortality in females. Its onset and prognosis are primarily concerned with persistent infection with high-risk types of human papillomavirus (HPV). However, the molecular mechanisms of HPV-positive CESC remain unclear. In this study, we conducted a high-throughput sequencing to identify differentially expressed miRNAs (DEMs). Besides, three series were selected from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs). Then the miRNA-TF-gene regulatory network was constructed using bioinformatic methods. Genes in the network were performed functional enrichment analysis and protein-protein interaction (PPI) network analysis. Ultimately, the expression levels of six key miRNAs, TFs, and mRNAs were validated by 20 HPV-positive CESC tissues and 15 normal cervical samples. A total of 52 DEMs and 300 DEGs differed between the HPV-positive CESC and normal cervical samples. Then the miRNA-TF-gene regulatory network was constructed consisting of 22 miRNAs, 6 TFs, and 76 corresponding genes, among which miR-149-5p, miRNA-1248 and E2F4 acted as key regulators. PPI network analysis showed that ten genes including TOP2A, AURKA, CHEK1, KIF11, MCM4, MKI67, DTL, FOXM1, SMC4, and FBXO5 were recognized as hub genes with the highest connectivity degrees. Besides, five key molecules miRNA-149-5p, E2F4, KIF11, DTL, and SMC4 were suggested to play crucial roles in the development of HPV-positive CESC. These results present a unique insight into the pathological mechanisms of HPV-positive CESC and possibly provides potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Immunogenic cell death (ICD) can be triggered by various therapies to induce anti-tumor immune responses, significantly enhancing treatment effectiveness, and is widely utilized in tumor immunotherapy., Methods: LUAD data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) validated ICD-related molecular subtypes via consensus clustering. Clinical features, ICD genes, driver genes, mutations, tumor microenvironment, immune checkpoints, and drug sensitivity were compared. RT-qPCR, Western blot, immunofluorescence, ELISA, flow cytometry, and tube formation assays validated findings., Results: Differential expression of 33 ICD genes was observed between tumor and normal tissues. These genes were clustered into two groups via consensus clustering and validated with GEO data. Prognostic analysis indicated superior outcomes in cluster 2 across TCGA and GEO cohorts. Significant disparities in clinicopathological characteristics like stage, gender, and age were noted between subtypes. Cluster 2 exhibited heightened expression of ICD-related genes, driver genes, immune checkpoints, and immune cells. Cluster 2 also showed increased sensitivity to chemotherapy drugs. IFNG overexpression in A549 and H1299 cells induced CRT exposure, HMGB1 release, and ATP secretion, thereby promoting dendritic cell maturation and enhancing CD8+ T cell function. Additionally, IFNG boosted tumor angiogenesis via HMGB1 pathways, which could be mitigated by HMGB1 inhibition., Conclusion: Identification of novel ICD-related molecular subtypes holds promise for guiding personalized therapies, assessing prognosis, and predicting immunotherapy efficacy in LUAD. IFNG emerges as a potential prognostic biomarker and therapeutic target, influencing both the tumor microenvironment and angiogenesis. These findings offer new insights into therapeutic strategies targeting IFNG-mediated pathways in LUAD., (© 2025 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Breast cancer (BRCA) remains the most prevalent cancer worldwide and the tumor microenvironment (TME) has been discovered to exert a wide influence on the overall survival and therapeutic response. Numerous lines of evidence reported that the effects of immunotherapy of BRCA were manipulated by TME. Immunogenic cell death (ICD) is a form of regulated cell death (RCD) that is capable of fueling adaptive immune responses and aberrant expression of ICD-related genes (ICDRGs) can govern the TME system by emitting danger signals or damage-associated molecular patterns (DAMPs). In the current study, we obtained 34 key ICDRGs in BRCA. Subsequently, using the transcriptome data of BRCA from the TCGA database, we constructed a risk signature based on 6 vital ICDRGs, which had a good performance in predicting the overall survival of BRCA patients. We also examined the efficacy of our risk signature in the validation dataset (GSE20711) in the GEO database and it performed excellently. According to the risk model, patients with BRCA were divided into high-risk and low-risk groups. Also, the unique immune characteristics and TME between the two subgroups and 10 promising small molecule drugs targeting BRCA patients with different ICDRGs risk have been investigated. The low-risk group had good immunity indicated by T cell infiltration and high immune checkpoint expression. Moreover, the BRCA samples could be divided into three immune subtypes according to immune response severity (ISA, ISB, and ISC). ISA and ISB predominated in the low-risk group and patients in the low-risk group exhibited a more vigorous immune response. In conclusion, we developed an ICDRGs-based risk signature that can predict the prognosis of BRCA patients and offer a novel therapeutic strategy for immunotherapy, which would be of great significance in the BRCA clinical setting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhao, Wang, Pan, Lv, He, Lian, Ma, Zhang, Yu, Zhao, Guo, Huang and Peng.)

Corneal ulcer is the most common symptom of corneal disease, which is one of the main causes of corneal blindness. The accurate classification of corneal ulcer has important clinical importance for the diagnosis and treatment of the disease. To achieve this, we propose a deep learning method based on multi-scale information fusion and label smoothing strategy. Firstly, the proposed method utilizes the densely connected network (DenseNet121) as backbone for feature extraction. Secondly, to fully integrate the shallow local information and the deep global information and improve the classification accuracy, we develop a multi-scale information fusion network (MIF-Net), which uses multi-scale information for joint learning. Finally, to reduce the influence of the inter-class similarity and intra-class diversity on the feature representation, the learning strategy of label smoothing is introduced. Compared with other state-of-the-art classification networks, the proposed MIF-Net with label smoothing achieves high classification performance, which reaches 87.07 and 83.84% for weighted-average recall (W&#95;R) on the general ulcer pattern and specific ulcer pattern, respectively. The proposed method holds promise for corneal ulcer classification in fluorescein staining slit lamp images, which can assist ophthalmologists in the objective and accurate diagnosis of corneal ulcer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lv, Peng, Wang and Wu.)

Background: Ferroptosis, a form of cell death driven by iron-dependent lipid peroxidation, may be a potential treatment for many cancers, including cervical cancer (CC). However, the regulation of long noncoding RNAs (lncRNAs) in the process of ferroptosis and whether ferroptosis inducers could increase the cytotoxicity of conventional chemotherapy drugs remain to be further elucidated., Methods: We analyzed the variation of 55 differentially ferroptosis-related genes (FRGs) and the influence of mutations in CC patients. The patients with CC were classified into two ferroptosis clusters by the non-negative matrix factorization (NMF) algorithm. The principal components analysis (PCA) was used to measure the ferroptosis score (FerroScore) in patients with CC. Besides, FerroScore was used to predict the sensitivity of chemotherapy and responses to immunotherapy in patients with CC. Finally, experiments were performed to verify the regulatory effect of AC026790.1 on erastin-induced ferroptosis, as well as the effect of erastin in combination with cisplatin on the toxicity of CC cells (SiHa, HeLa)., Result: There were significant differences in the overall survival and immune cell infiltration between the two ferroptosis clusters. Patients with low FerroScore were more sensitive to chemotherapy drugs such as cisplatin and docetaxel. The low-FerroScore group had higher CD8+ T cell infiltration and immune checkpoint expression, demonstrating that patients with lower FerroScores were more sensitive to immunotherapy, which was consistent with the result of the submap method. In vitro, overexpression of AC026790.1 could promote erastin-induced ferroptosis, and the combination of erastin and cisplatin could increase the toxicity of CC cells., Conclusion: FerroScore has a potential prognostic value for CC that may provide a reference for chemotherapy and immunotherapy. LncRNA AC026790.1 can influence ferroptosis, and the combination of ferroptosis inducers and chemotherapy drugs can provide a new perspective on cancer treatment., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Pengxiang Li et al.)

The incidence and mortality of colorectal cancer (CRC) are increasing year by year. The accurate classification of CRC can realize the purpose of personalized and precise treatment for patients. The tumor microenvironment (TME) plays an important role in the malignant progression and immunotherapy of CRC. An in-depth understanding of the clusters based on the TME is of great significance for the discovery of new therapeutic targets for CRC. We extracted data on CRC, including gene expression profile, DNA methylation array, somatic mutations, clinicopathological information, and copy number variation (CNV), from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) (four datasets-GSE14333, GSE17538, GSE38832, and GSE39582), cBioPortal, and FireBrowse. The MCPcounter was utilized to quantify the abundance of 10 TME cells for CRC samples. Cluster repetitive analysis was based on the Hcluster function of the Pheatmap package in R. The ESTIMATE package was applied to compute immune and stromal scores for CRC patients. PCA analysis was used to remove batch effects among different datasets and transform genome-wide DNA methylation profiling into methylation of tumor-infiltrating lymphocyte (MeTIL). We evaluated the mutation differences of the clusters using MOVICS, DeconstructSigs, and GISTIC packages. As for therapy, TIDE and SubMap analyses were carried out to forecast the immunotherapy response of the clusters, and chemotherapeutic sensibility was estimated based on the pRRophetic package. All results were verified in the TCGA and GEO data. Four immune clusters (ImmClust-CS1, ImmClust-CS2, ImmClust-CS3, and ImmClust-CS4) were identified for CRC. The four ImmClusts exhibited distinct TME compositions, cancer-associated fibroblasts (CAFs), functional orientation, and immune checkpoints. The highest immune, stromal, and MeTIL scores were observed in CS2, in contrast to the lowest scores in CS4. CS1 may respond to immunotherapy, while CS2 may respond to immunotherapy after anti-CAFs. Among the four ImmClusts, the top 15 markers with the highest mutation frequency were acquired, and CS1 had significantly lower CNA on the focal level than other subtypes. In addition, CS1 and CS2 patients had more stable chromosomes than CS3 and CS4. The most sensitive chemotherapeutic agents in these four ImmClusts were also found. IHC results revealed that CD29 stained significantly darker in the cancer samples, indicating that their CD29 was highly expressed in colon cancer. This work revealed the novel clusters based on TME for CRC, which would guide in predicting the prognosis, biological features, and appropriate treatment for patients with CRC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zheng, Ma, Bai, Huang, Lv, Deng, Wang, Lian, Tong, Zhang, Yue, Zhang, Li and Peng.)

Background: Head and neck squamous cell carcinoma (HNSCC) is a frequently lethal malignancy, and the mortality is considerably high. The tumor microenvironment (TME) has been identified as a critical participation in cancer development, treatment, and prognosis. However, competing endogenous RNA (ceRNA) networks grouping with immune/stromal scores of HNSCC patients need to be further illustrated. Therefore, our study aimed to provide clues for searching promising prognostic markers of TME in HNSCC., Materials and Methods: ESTIMATE algorithm was used to calculate immune scores and stromal scores of the enrolled HNSCC patients. Differentially expressed genes (DEGs), lncRNAs (DELs), and miRNAs (DEMs) were identified by comparing the expression difference between high and low immune/stromal scores. Then, a ceRNA network and protein-protein interaction (PPI) network were constructed for selecting hub regulators. In addition, survival analysis was performed to access the association between immune scores, stromal scores, and differentially expressed RNAs in the ceRNA network and the overall survival (OS) of HNSCC patients. Then, the GSE65858 datasets from Gene Expression Omnibus (GEO) database was used for verification. At last, the difference between the clinical characteristics and immune cell infiltration in different expression groups of IL10RA, PRF1, and IL2RA was analyzed., Results: Survival analysis showed a better OS in the high immune score group, and then we constructed a ceRNA network composed of 97 DEGs, 79 DELs and 22 DEMs. Within the ceRNA network, FOXP3, IL10RA, STAT5A, PRF1, IL2RA, miR-148a-3p, miR-3065-3p, and lncRNAs, including CXCR2P1, HNRNPA1P21, CTA-384D8.36, and IGHV1OR15-2, were closely correlated with the OS of HNSCC patients. Especially, using the data from GSE65858, we successfully verified that IL10RA, PRF1, and IL2RA were not only significantly upregulated in patients high immune scores, but also their high expressions were associated with longer survival time. In addition, stratified analysis showed that PRF1 and IL2RA might be involved in the mechanism of tumor progress., Conclusion: In conclusion, we constructed a ceRNA network related to the TME of HNSCC, which provides candidates for therapeutic intervention and prognosis evaluation., Competing Interests: The authors declared no potential conflicts of interests., (Copyright © 2022 Shuai Zhao et al.)

Although recent clinical investigations emphasize the roles of myriad diversities of RNAs in stromal and immune components in the tumor microenvironment, especially in colon adenocarcinoma, however, analyses of "competing endogenous RNAs (ceRNA)" network in association with stromal and immune scores have yet to be determined. This study was conducted to explore the regulatory mechanisms of a stromal-immune score-based ceRNA network in colon adenocarcinoma. Stromal and immune scores of colon adenocarcinoma tumor samples were calculated by using the ESTIMATE algorithm. Differential expression analysis between samples with high/low stromal and immune scores was performed, followed by functional annotation for the overlapping DEmRNAs. The ceRNA network was constructed by differential expression analysis, prediction of RNA-RNA interaction, and correlation with clinicopathological parameters of the patients, which were further verified by external datasets and experiments. Colon adenocarcinoma patients having higher immune scores exhibited prolonged overall survival. RNA dataset analyses from TCGA revealed aberrant expressions of a total of 2052 mRNAs, 108 lncRNAs, and 70 miRNAs between high and low stromal/immune groups. Functional annotation mapped the differentially overexpressed mRNAs for immune-associated GO terms. To construct the ceRNA network, a total of 48 lncRNAs, 40 miRNAs, and 199 mRNAs were sorted out. A dysregulated ceRNA network consisting of 6 lncRNAs, 11 miRNAs, and 39 mRNAs was constructed by comparing RNA expressions between cancer as well as adjacent normal tissues. The ceRNA regulatory axis "MIAT/miR-532-3p/STC1" was regarded as a potential hit by the comprehensive analysis. The RT-qPCR assay showed upregulation of MIAT and STC1 while downregulation of hsa-miR-532-3p expression in cancer. Thus, our study highlights the potential role of a stromal-immune score-based ceRNA network in the colon adenocarcinoma microenvironment. The ceRNA axis MIAT/miR-532-3p/STC1 could serve as a promising therapeutic target for colon adenocarcinoma., Competing Interests: All authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yalin Tong et al.)

Background: Breast cancer (BC) is a highly heterogeneous disease with high morbidity and mortality. Its subtypes may have distinctly different biological behaviors, clinical outcomes, and therapeutic responses. The metabolic status of BC tissue is closely related to its progress. Therefore, we comprehensively characterized the function of metabolic genes in BC and identified new biomarkers to predict BC patients' prognoses., Methods: Metabolic genes were identified by intersecting genes obtained from two published pieces of literature. The function of metabolic genes in BC was determined by extracting differentially expressed genes (DEGs), performing functional enrichment analyses, analyzing the infiltrating proportion of immune cells, and conducting metabolic subgroup analyses. A risk score model was constructed to assess the prognoses of BC patients by performing the univariate Cox regression, LASSO algorithm, multivariate Cox regression, Kaplan-Meier survival analyses, and ROC curve analyses in the training set. The prognostic model was then validated on the testing dataset, external dataset, the whole TCGA-BC database, and our clinical specimens. Finally, a nomogram was constructed for clinical prognostic prediction based on the risk score model and other clinicopathological parameters., Results: 955 metabolic genes were obtained. Among these, 157 metabolic DEGs were identified between BC and normal tissues for subsequent GO and KEGG pathway enrichment analyses. 5 metabolic genes were negatively correlated with CD8 + T cells, while 49 genes were positively correlated with CD8 + T cells. Furthermore, 5 metabolic subgroups with varying proportions of PAM50 subtypes, TNM classification, and immune cell infiltration were obtained. Finally, a risk score model was constructed to predict the prognoses of BC patients, and a nomogram incorporating the risk score model was established for clinical application., Conclusion: In this study, we elucidated tumor heterogeneity from metabolite profiling of BC. The roles of metabolic genes in the occurrence of BC were comprehensively characterized, clarifying the relationship between the tumor microenvironment (TME) and metabolic genes. Meanwhile, a concise prediction model was also constructed based on metabolic genes, providing a convenient and precise method for the individualized diagnosis and treatment of BC patients., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2022 Ruijing Yu et al.)

Multiple myeloma (MM) is an extremely complex plasma cell malignancy that is genetically heterogeneous. A recent Genome-wide association study (GWAS) indicated that variation at 2q22 (rs61070260) influences MM risk. This association has not been validated to date in a Chinese Han population. In this study, we evaluated the association between rs61070260 in LRP1B and MM risk in a Chinese Han population involving 739 MM patients and 592 healthy controls. Our results indicated that rs61070260 in LRP1B was significantly associated with MM susceptibility (P=3.937×10 -37 ). Furthermore, the linkage disequilibrium (LD) analysis of rs61070260 revealed an LD block encompassing exons 26, 27 and 28 of the LRP1B gene, and a subsequent sequencing analysis identified three SNPs (rs762074421, rs756168629, rs113600691) in exons 26 and 28 of LRP1B . For the SNP rs756168629 in exon 26, a missense mutation which results in a transition from arginine to histidine at position 1661 of the LRP1B protein, has not been found in Chinese populations according to the Chinese Millionome Database and Genome Aggregation Database (EAS), and this mutation was predicted to be deleterious or damaging by SIFT and PolyPhen. These findings firmly establish the role of LRP1B in contributing to MM susceptibility. In addition, the identification of a rare coding mutation (p.R1661H) in LRP1B detected in MM individuals was suggested to be harmful to the encoded protein, which was characterized as a candidate tumour suppressor; thus, LRP1B is likely to be a disease-associated gene that is implicated in the development and progression of MM., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Excision repair cross-complementation group 1 (ERCC1), a DNA repair protein, is vital for maintaining genomic fidelity and integrity. Despite the fact that a mounting body of case-control studies has concentrated on investigating the association of the ERCC1 rs11615 polymorphism and breast cancer risk, there is still no consensus on it. We conducted the current meta-analysis of all eligible articles to reach a much more explicit conclusion on this ambiguous association. A total of seven studies involving 2354 breast cancer cases and 2193 controls were elaborately selected for this analysis from the Embase, EBSCO, PubMed, WanFang, and China National Knowledge Infrastructure (CNKI) databases. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated in our meta-analysis. We found that the ERCC1 rs11615 polymorphism was significantly associated with breast cancer risk under all genetic models. When excluded, the studies that deviated from Hardy-Weinberg equilibrium (HWE), the pooled results of what remained significantly increase the risk of breast cancer under the allele model (OR = 1.14, 95% CI = 1.02-1.27, P =0.02), heterozygote model (OR = 1.24, 95% CI = 1.06-1.44, P =0.007), and dominant model (OR = 1.21, 95% CI = 1.05-1.41, P =0.01). This increased breast cancer risk was found in Asian population as well as under the heterozygote model (OR = 1.24, 95% CI = 1.05-1.48, P =0.013) and dominant model (OR = 1.20, 95% CI = 1.02-1.42, P =0.03). Our results suggest that the ERCC1 rs11615 polymorphism is associated with breast cancer susceptibility, and in particular, this increased risk of breast cancer existence in Asian population., (© 2018 The Author(s).)

MicroRNAs play critical roles in the occurrence and progression in various cancers including colorectal cancer. Here, we found that microRNA-30a expression was significantly downregulated in colorectal cancer tissues compared to adjacent noncancerous tissues, and the suppression levels of microRNA-30a were significantly associated with tumor differentiation and lymph node metastasis. We also discovered that the expression level of microRNA-30a was inversely proportional to the invasive potential of several colorectal cancer cell lines. Moreover, overexpression of microRNA-30a in colorectal cancer cells inhibited activity of cell migration and invasion. Luciferase reporter assay confirmed metadherin could be a direct target of microRNA-30a, as the overexpression of microRNA-30a decreased metadherin expression at both the protein and messenger RNA levels. Furthermore, the knockdown of metadherin expression in SW620 significantly decreased cell metastasis and invasion. The upregulation of metadherin at the protein level negatively correlated with the expression of microRNA-30a in colorectal cancer tissues, and this upregulation could partially attenuate the effect induced by microRNA-30a. These findings indicate that microRNA-30a may act as a tumor suppressor in colorectal cancer and that microRNA-30a represses cell migration and invasion by decreasing metadherin, highlighting the therapeutic potential of microRNA-30a and metadherin in colorectal cancer treatment.