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Accumulated evidence indicates that rare variants exert a vital role on predisposition and progression of human diseases, which provides neoteric insights into disease etiology. In the current study, based on three independently retrospective studies of 5,016 lung cancer patients and 5,181 controls, we analyzed the associations between five rare polymorphisms (i.e., p.Glu116Lys, p.Asn118Ser, p.Arg138Cys, p.Ala195Thr and p.Leu259Phe) in MKK7 and lung cancer risk and prognosis. To decipher the precise mechanisms of MKK7 rare variants on lung cancer, a series of biological experiments was further performed. We found that the MKK7 p.Glu116Lys rare polymorphism was significantly associated with lung cancer risk, progression and prognosis. Compared with Glu/Glu common genotype, the 116Lys rare variants (Lys/Glu/+ Lys/Lys) presented an adverse effect on lung cancer susceptibility (odds ratio [OR] = 3.29, 95% confidence interval [CI] = 2.70-4.01). These rare variants strengthened patients' clinical progression that patients with 116Lys variants had a significantly higher metastasis rate and advanced N, M stages at diagnosis. In addition, the patients with 116Lys variants also contributed to worse cancer prognosis than those carriers with Glu/Glu genotype (hazard ratio [HR] = 1.53, 95% CI = 1.32-1.78). Functional experiments further verified that the MKK7 p.116Lys variants altered the expression of several cancer-related genes and thus affected lung cancer cells proliferation, tumor growth and metastasis in vivo and in vitro. Taken together, our findings proposed that the MKK7 p.Glu116Lys rare polymorphism incurred a pernicious impact on lung cancer risk and prognosis through modulating expressions of a serial of cancer-related genes.

Breast cancer, as a malignant tumor threatening the survival of women in China, its incidence rate is increasing year by year and showing a younger trend, control of cancer cell proliferation, invasion, metastasis is the focus and difficulty of treatment. DEAD-box polypeptide 5 (DDX5), a processing factor regulating RNA biological function, is a multi-dimensional functional protein involved in regulating RNA splicing, ribosome biological function, transcription and translation. It can promote the proliferation, invasion and metastasis of breast cancer through gene amplification, activation of carcinogens, enhancement of epithelial mesenchymal transformation, and reorganization of cytoskeleton. It can also be used as a marker of prognosis and recurrence of breast cancer. This article reviews the role of DDX5 in promoting the proliferation, invasion and metastasis of breast cancer, its significance in the classification, prognosis and recurrence of breast cancer, and the clinical reports of existing Chinese medicine intervention DDX5 on breast cancer, which can provide a new perspective for the exploration of the etiology of breast cancer and new targeted therapy ideas.

Background: This study aims to assess whether sarcopenia can be used to predict prognosis in patients with heart failure (HF) and if different diagnostic criteria for sarcopenia and diverse regions where studies were conducted could affect prognostic outcomes, thus providing a preliminary basis for early identification and prediction of poor prognosis in HF. Methods: The PubMed, Cochrane, Embase, and CNKI (China National Knowledge Infrastructure) databases were searched from inception until March 2023. Cohort studies evaluating the prognostic effect of sarcopenia in patients with HF were included. Two authors independently assessed the studies according to the Newcastle-Ottawa Scale. The meta-analyses were performed using RevMan 5.3 software. The study results were reported using a checklist of Preferred Reporting Items for Systematic Reviews and Meta-analyses were used to report the study results. Results: A total of 12 studies with 3696 HF patients were included. The results showed that the sarcopenia population had a higher risk of all-cause mortality (HR (hazard ratio) = 1.98, 95% CI (confidence interval): 1.61–2.44) and major adverse cardiovascular events (MACE) (HR = 1.24, 95% CI: 1.06–1.45) compared to the non-sarcopenia population. Moreover, the subgroup analysis reported that different diagnostic criteria for sarcopenia and diverse regions were statistically significant for all-cause mortality, except for the Europe subgroup (HR = 1.34, 95% CI: 0.89–2.02). In the subgroup analysis of MACE, all subgroups were statistically significant except for the European Working Group on Sarcopenia in Older People (EWGSOP) (HR = 1.39, 95% CI: 0.86–2.25) and European subgroups (HR = 1.39, 95% CI: 0.86–2.25). Conclusions: Sarcopenia is associated with poor prognosis, including all-cause mortality and MACE, in patients with HF. However, due to the adoption of various diagnostic criteria in different regions of the world, these results need further validation.

Abstract Background Colon adenocarcinoma (COAD) is a gastrointestinal tumor with a high degree of malignancy. Its deterioration process is closely related to the tumor microenvironment, and transcription factors (TF) play a regulatory role in this process. Currently, there is a lack of exploration between the genes related to the COAD tumor microenvironment and the survival prognosis of patients. Models composed of multiple genes usually predict the survival prognosis of patients more accurately than single genes. We can analyze the multigene models that can predict the prognosis of COAD from the current database. Methods The limma package of the R programming language is used for gene differential expression analysis. Kaplan-Meier curve is used to analyze the relationship between the patient risk score model and survival data. The hazard model is used to analyze the relationship between the risk score and the clinical data of COAD patients. The information of immune genes and immune cells is obtained from IMMPORT database and TIMER database. Receiver operating characteristic (ROC) curve is used to judge the stability of the model. Results We found 7 immune genes, which can built a risk score model to predict the survival prognosis of COAD. According to univariate and multivariate analysis, the risk score can be used as an independent predictor. The content of some immune microenvironment cells will also increase as the risk score increases. Conclusions We found 7 immune genes, such as SLC10A2 (solute carrier family 10 member 2), CXCL3 (C-X-C motif chemokine ligand 3), IGHV5-51 (immunoglobulin heavy variable 5-51), INHBA (inhibin subunit beta A), STC1 (stanniocalcin 1), UCN (urocortin), and OXTR (oxytocin receptor), can constitute a model for predicting the prognosis of COAD. They may provide potential therapeutic targets for clinical treatment of COAD.

Temporal muscle thickness measured on 3D MRI has recently been linked to prognosis in glioblastoma patients and may serve as an independent prognostic indicator. This single-center study looked at temporal muscle thickness and prognosis in patients with primary glioblastoma. Overall survival was the major study outcome. For a retrospective analysis from 2010 to 2020, clinical data from 102 patients with glioblastoma at the Department of Oncology Radiotherapy of the First Affiliated Hospital of Dalian Medical University were gathered. Fifty-five cases from 2016 to 2020 contained glioblastoma molecular typing data, of which 45 were IDH wild-type glioblastomas and were analysed separately. TMT was measured on enhanced T1-weighted magnetic resonance images in patients with newly diagnosed glioblastoma.Overall patient survival (OS) was calculated by the Kaplan–Meier method and survival curves were plotted using the log-rank-sum test to determine differences between groups, and multifactorial analyses were performed using a Cox proportional-risk model.The median TMT for 102 patients was 6.775 mm (range: 4.95–10.45 mm). Patients were grouped according to median TMT, and the median overall survival (23.0 months) was significantly longer in the TMT > median group than in the TMT median group (P 0.001; Log-rank test). Analysing 45 patients with IDH wild type alone, the median overall survival (12 months) of patients in the TMT > median group was significantly longer than that of patients in the TMT ≤ median group (8 months) (P < 0.001; Log-rank test).TMT can serve as an independent prognostic factor for glioblastoma. [ABSTRACT FROM AUTHOR]

Background: Cellular senescence frequently occurs during anti-cancer treatment, and persistent senescent tumor cells (STCs) unfavorably promote tumor progression through paracrine secretion of the senescence-associated secretory phenotype (SASP). Extracellular vesicles (EVs) have recently emerged as a novel component of the SASP and primarily mediate the tumor-promoting effect of the SASP. Of note, the potential effect of EVs released from STCs on tumor progression remains largely unknown. Methods: We collected tumor tissues from two cohorts of colorectal cancer (CRC) patients to examine the expression of p16, p21, and SERPINE1 before and after anti-cancer treatment. Cohort 1 included 22 patients with locally advanced rectal cancer (LARC) who received neoadjuvant therapy before surgical resection. Cohort 2 included 30 patients with metastatic CRC (mCRC) who received first-line irinotecan-contained treatment. CCK-8, transwell, wound-healing assay, and tumor xenograft experiments were carried out to determine the impacts of EVs released from STCs on CRC progression in vitro and in vivo. Quantitative proteomic analysis was applied to identify protein cargo inside EVs secreted from STCs. Immunoprecipitation and mass spectrometer identification were utilized to explore the binding partners of SERPINE1. The interaction of SERPINE1 with p65 was verified by co-immunoprecipitation, and their co-localization was confirmed by immunofluorescence. Results: Chemotherapeutic agents and irradiation could potently induce senescence in CRC cells in vitro and in human CRC tissues. The more significant elevation of p16 and p21 expression in patients after anti-cancer treatment displayed shorter disease-free survival (DFS) for LARC or progression-free survival (PFS) for mCRC. We observed that compared to non-STCs, STCs released an increased number of EVs enriched in SERPINE1, which further promoted the progression of recipient cancer cells. Targeting SERPINE1 with a specific inhibitor, tiplaxtinin, markedly attenuated the tumor-promoting effect of STCs-derived EVs. Additionally, the patients with greater increment of SERPINE1 expression after anti-cancer treatment had shorter DFS for LARC or PFS for mCRC. Mechanistically, SERPINE1 bound to p65, promoting its nuclear translocation and subsequently activating the NF-κB signaling pathway. Conclusions: We provide the in vivo evidence of the clinical prognostic implications of therapy-induced senescence. Our results revealed that STCs were responsible for CRC progression by producing large amounts of EVs enriched in SERPINE1. These findings further confirm the crucial role of therapy-induced senescence in tumor progression and offer a potential therapeutic strategy for CRC treatment. [ABSTRACT FROM AUTHOR]

Purpose: There is an aberrant expression of NBAT-1 in various human cancers, which was proven to limit the proliferation, invasion, and metastasis of tumour cells via multiple approaches. Most existing research focuses on sample size and discrete outcomes. Thus, a quantitative meta-analysis was performed to elucidate the prognostic value of lncRNA NBAT-1 expression in cancer patients. Materials and methods: Using Web of Science and PubMed, two researchers independently identified relevant studies to explore the association between the pathological features of human cancers and NBAT-1 expression levels. Then two scholars conducted literature screening according to exclusion criteria and admission criteria, and finally conducted statistical analysis through data extraction with StataSE 12.0. Results: A total of 12 eligible studies with 1600 patients were included in the meta-analysis eventually. It is indicated that the low expression level of lncRNA NBAT-1 was closely related to distant metastasis [RR = 0.50, 95% CI (0.33, 0.76), and P = 0.00], deep tumour invasion [RR = 0.62, 95% CI (0.49,0.80), and P = 0.00], poor histological grade [RR = 0.68, 95% CI (0.57, 0.81), and P = 0.00], advanced TNM stage [RR = 0.66, 95% CI (0.55, 0.79), and P = 0.00], large tumour volume[RR = 0.72, 95% CI (0.55, 0.93), and P = 0.01], and lymph node metastasis [RR = 0.62, 95% CI (0.46, 0.84), and P = 0.00], suggesting that it may serve as biomarkers for patients with poor prognosis. Conclusion: Reduced expression of NBAT-1 can predict poor prognosis in several cancers, as found in the meta-analysis, demonstrating that NBAT-1 can serve as a promising prognostic factor of human cancers. [ABSTRACT FROM AUTHOR]

Objective. To determine prognostic role of endothelial progenitor cells (EPCs) in intensive care patients with acute myocardial infarction (AMI). Materials and Methods. From December 2018 to July 2021, a total of 91 eligible patients with AMI were consecutively examined in a single intensive care unit (ICU) in China. Patients with a history of acute coronary artery disease were excluded from the study. Samples were collected within 24 hr of onset of symptoms. EPCs, defined as coexpression of CD34+/CD133+ cells or CD133+/CD34+/KDR+, were studied using flow cytometry and categorized by quartiles. Based on the 28-days mortality outcome, the patients were further divided into two groups: death and survival. The study incorporated various variables, including cardiovascular risk factors such as body mass index, hypertension, diabetes, hypercholesterolemia, atherosclerotic burden, and medication history, as well as clinical characteristics such as APACHEⅡscore, central venous-arterial carbon dioxide difference (GAP), homocysteine, creatinine, C-reactive protein, HbAlc, and cardiac index. Cox regression analysis was employed to conduct a multivariate analysis. Results. A total of 91 patients with AMI who were admitted to the ICU were deemed eligible for inclusion in the study. Among these patients, 23 (25.3%) died from various causes during the follow-up period. The counts of EPCs were found to be significantly higher in the survival group compared to the death group (P < 0.05). In the univariate analysis, it was observed that the 28-days mortality rate was associated with the several factors, including the APACHEⅡscore (P = 0.00), vasoactive inotropic score (P = 0.03), GAP (P = 0.00), HCY (P = 0.00), creatinine (P = 0.00), C-reactive protein (P = 0.00), HbAlc (P = 0.00), CI (P = 0.01), quartiles of CD34+/CD133+ cells (P = 0.00), and quartiles of CD34+/CD133+/KDR+ cells (P = 0.00). CD34+/CD133+/KDR+ cells retained statistical significance in Cox regression models even after controlling for clinical variables (HR: 6.258 × 10−10 and P = 0.001). Nevertheless, no significant correlation was observed between CD34+/CD133+ cells and all-cause mortality. Conclusions. The decreased EPCs levels, especially for CD34+/CD133+/KDR+ cells subsets, were an independent risk factor for 28-days mortality in AMI patients. [ABSTRACT FROM AUTHOR]

Background: Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy with a high mortality rate and poor prognosis. The exploration and understanding of biomarkers will help to further improve the diagnosis and treatment of OSCC.Methods: Tumor tissue samples from 319 OSCC patients were retrospectively collected, along with their clinical information. In combination with bioinformatics tools and multiplex immunohistochemistry (mIHC) analyses, we evaluated NUP62CL protein expression and its relationship to tumor-infiltrating immune cells (TIICs) and immune checkpoints in the tumor microenvironment (TME), as well as its association with clinical features and prognosis of OSCC.Results: We identified high-NUP62CL expression in OSCC tissues, and high-NUP62CL protein expression was associated with large tumor size, advanced clinical stage and poor prognosis. In addition, NUP62CL protein expression was positively associated with the abundance of CD3+CD4+ T cells (P< 0.01), CD3+CD8+ T cells (P< 0.01), CD56+ NK cells (P< 0.05), CD68+CD86+ macrophages (P< 0.01) and CD68+CD163+ macrophages (P< 0.01), as well as the immune checkpoints, including PD-1 (P< 0.001), PD-L1 (P< 0.001), and CTLA-4 (P< 0.001) protein expression.Conclusion: In conclusion, NUP62CL could be an effective prognostic and immunological biomarker for OSCC patients. [ABSTRACT FROM AUTHOR]

Background: We screened out several hypermethylated solute carrier (SLC) family genes in acute myeloid leukemia by reduced representation bisulfite sequencing. SLC22A3 encodes an organic cation transport protein, which is critical for drug transportation and cellular detoxification. SLC22A3 is significantly downregulated and associated with tumor progression and worse prognosis in a variety of solid tumors. However, there are no data available regarding the role of SLC22 in AML. This study aimed to explore the regulatory mechanism of DNA methylation on SLC22A3 expression, as well as its clinical significance in AML prognosis. Results: SLC22A3 was identified as the sole prognosis-associated gene among SLCs based on TCGA and Beat AML databases. Bone marrow mononuclear cells (BMMNCs) from AML, MDS patients, and healthy donors were enrolled in this study. SLC22A3 methylation was significantly increased in AML compared with controls and MDS patients; meanwhile, the expression level of SLC22A3 was decreased. SLC22A3 hypermethylation presented an obvious association with some specific clinical characteristics and affected the survival time of AML patients as an independent risk indicator. SLC22A3 expression changed regularly as the disease complete remissions and relapses. Demethylation drug 5-aza-2′-deoxycytidine (DAC) activated transcription and increased mRNA expression of SLC22A3 in leukemia cell lines and AML fresh BMMNCs. Knockdown of SLC22A3 in leukemia cells enhanced cell proliferation and suppressed cell apoptosis. Data from public programs were used for auxiliary screening of probable molecular mechanisms of SLC22A3 in the antileukemia effect. Conclusions: Our results showed that increased methylation and decreased expression of SLC22A3 may be indicators of poor prognosis in AML. Methylation-silenced SLC22A3 expression may have potential guiding significance on antileukemia effect of DAC. [ABSTRACT FROM AUTHOR]

Background: Smith-like (LSM) family members play critical roles in multiple oncologic processes in several types of malignancies. The study on LSM family members of HCC might provide new insights into the tumorigenesis and therapeutic strategies of HCC. Methods: The clinical significance and oncologic biological functions of LSM family members were assessed through multiple bioinformatics methods and in vitro studies. The potential correlation between LSM family members and tumor immunity was also investigated using single sample gene set enrichment analysis (ssGSEA) and the ESTIMATE algorithm. Results: LSM family member overexpression in HCC was significantly correlated with poor clinical outcomes such as higher TNM stage, advanced histologic grade, and worse prognosis. A risk score system based on LSM5, LSM10, LSM12, and LSM14B showed a reliable predictive ability for OS of HCC patients. Functional enrichment analysis demonstrated that LSM family members overexpressed were all involved in cell cycle related biological processes. Besides, LSM12, LSM14A, and LSM14B were found to be significantly associated with PI3K-Akt-mTOR and T cell receptor signaling pathways. Tumors with LSM12, LSM14A, and LSM14B overexpression exhibited lower infiltration of activated CD8+ T cells with declined cytolytic activity and immune score, but increased infiltration of Th2 cells and Th2/Th1. LSM12, LSM14A, and LSM14B overexpression is also associated with higher tumor-related immune checkpoints (e.g., PD-L1, B7-H3, and PVR) expression and increased therapeutic insensitivity to immune checkpoint blockade (ICB). Moreover, the knockdown of LSM12, LSM14A, and LSM14B significantly inhibited the proliferation and invasion of HCC cells. Conclusion: This study systematically investigated the expression pattern and biological values of LSM family members in HCC and identified LSM family members as novel therapeutic targets in HCC. [ABSTRACT FROM AUTHOR]

Glioma is a brain tumor that arises in the central nervous system and is categorized according to histology and molecular genetic characteristics. Long non-coding RNAs (lncRNAs) are RNAs longer than 200 nucleotides in length. They have been reported to influence significant events such as carcinogenesis, progression, and increased treatment resistance on glioma cells. Long non-coding RNAs promote cell proliferation, migration, epithelial-to-mesenchymal transition and invasion in glioma cells. Various significant advancements in transcriptomic profiling studies have enabled the identification of immune-related long non-coding RNAs as immune cell-specific gene expression regulators that mediates both stimulatory and suppressive immune responses, implying lncRNAs as potential candidates for improving immunotherapy efficacy against tumors and due to the lack of different diagnostic and treatments for glioma, lncRNAs are potential candidates to be used as future diagnostic, prognostic biomarker and treatment tools for glioma. This review's primary purpose is to concentrate on the role of long non-coding RNAs in early glioma identification, treatment, and immunotherapy. [ABSTRACT FROM AUTHOR]

Breast cancer is a kind of malignant tumor that occurs in breast tissue, which is the most common cancer in women. Cellular metabolism is a critical determinant of the viability and function of cancer cells in tumor microenvironment. In this study, based on the gene expression profile of metabolism-related genes, the prognostic value of 20 metabolic pathways in patients with breast cancer was identified. A universal risk stratification signature that relies on 20 metabolic pathways was established and validated in training cohort, two testing cohorts and The Cancer Genome Atlas pan cancer cohort. Then, the relationship between metabolic risk score subtype, prognosis, immune infiltration level, cancer genotypes and their impact on therapeutic benefit were characterized. Results demonstrated that the patients with the low metabolic risk score subtype displayed good prognosis, high level of immune infiltration and exhibited a favorable response to neoadjuvant chemotherapy and immunotherapy. Taken together, the work presented in this study may deepen the understanding of metabolic hallmarks of breast cancer, and may provide some valuable information for personalized therapies in patients with breast cancer. [ABSTRACT FROM AUTHOR]

Objective. To explore the clinical implications of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) for diagnosing frailty in patients with maintenance hemodialysis (MHD) and their correlations with patient prognosis. Methods. A total of 185 patients with MHD admitted to the hemodialysis center of our hospital were selected, 72 of whom were diagnosed with frailty according to the Chinese version of Tilburg Frailty Indicator (TFI). The relevant data were collected, and the influencing factors of frailty in MHD patients were analyzed by one-way analysis of variance (ANOVA) and multivariate logistic regression. The value of NLR and PLR in diagnosing frailty in MHD patients was observed, and patients' all-cause mortality was compared during the 3-year follow-up. The influences of different levels of NLR and PLR on the survival of MHD patients were investigated. Results. Multivariate regression analysis identified that serum albumin, dialysis adequacy, NLR, and PLR are independent risk factors for frailty in MHD patients (P < 0.05). The area under the receiver operating characteristic (ROC) curve of NLR and PLR in diagnosing frailty in MHD patients was 0.859 and 0.799, respectively. Compared with the nonfrailty group, the 3-year mortality was higher, and the 3-year survival rate assessed by survival analysis was lower in the frailty group (P < 0.05). Patients with high NLR and PLR levels showed a lower 3-year survival rate. Conclusions. Dialysis adequacy, serum albumin, NLR, and PLR are independently associated with frailty in MHD patients. NLR and PLR are of a certain diagnostic value for frailty in MHD patients. MHD patients with frailty have an unfavorable prognosis, as of those with high NLR and PLR levels. [ABSTRACT FROM AUTHOR]

Background: Hypoxia plays a crucial role in immunotherapy of hepatocellular carcinoma (HCC) by changing the tumor microenvironment. Until now the association between hypoxia genes and prognosis of HCC remains obscure. We attempt to construct a hypoxia model to predict the prognosis in HCC.Results: We screened out 3 hypoxia genes (ENO1, UGP2, TPI1) to make the model, which can predict prognosis in HCC. And this model emerges as an independent prognostic factor for HCC. A Nomogram was drawn to evaluate the overall survival in a more accurate way. Furthermore, immune infiltration state and immunosuppressive microenvironment of the tumor were detected in high-risk patients.Conclusion: We establish and validate a risk prognostic model developed by 3 hypoxia genes, which could effectively evaluate the prognosis of HCC patients. This prognostic model can be used as a guidance for hypoxia modification in HCC patients undergoing immunotherapy. [ABSTRACT FROM AUTHOR]

Background. In recent years, the incidence of colorectal cancer (CRC) has continued to increase. Although the overall prognosis of CRC has improved with the continuous improvement of the level of treatment, the prognosis of metastatic colorectal cancer (mCRC) is still poor. The purpose of our study is to explore the prognostic value of platelet to lymphocyte ratio (PLR) in mCRC. Methods. The PubMed, Web of Science, and Embase (via OVID) were systematically searched to obtain all relevant research. We used hazard ratio (HR) with 95% confidence interval (CI) to assess the associations of PLR and overall survival (OS) and progression free survival (PFS). Results. A total of twelve studies containing 1452 patients were included in this meta-analysis. Pooled analysis showed that high levels of PLR were associated with poor OS (HR: 1.72, 95% CI: 1.27–2.33, and P < 0.01) and PFS (HR: 1.64, 95% CI: 1.16–2.31, and P = 0.033). Conclusion. Our analysis suggested that high levels of PLR pretreatment may be an effective predictive biomarker for the prognosis of mCRC patients. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer is one of the most common malignancy in the world. It has been reported that cancer stem cells (CSCs) serve as the primary drivers of tumorigenesis and tumor progression. There is an urgent need to explore novel molecules that regulate CSCs or their signatures. Increasing evidence has shown that miRNAs are involved in tumorigenesis and progression. Here, we aim to explore the regulatory effect and mechanism of miR-3065-3p on the stemness of colorectal cancer.Methods: The expression of miR-3065-3p in colorectal cancer and the association of miR-3065-3p expression with prognosis of patients with colorectal cancer were analyzed using TCGA dataset or clinical cases. Gain or loss of function in different models, including colorectal cancer cell lines and orthotopic xenograft or liver metastatic mouse model, were used to investigate the effects of miR-3065-3p on colorectal cancer stemness and metastasis in vitro and in vivo. Cancer stemness was analyzed by detecting the ability of migration and invasion, NANOG, OCT4, and SOX2 expression, ALDH activity and sphere formation. In addition, the interaction of miR-3065-3p and cytokine receptor-like factor 1 (CRLF1) was analyzed theoretically and identified by the luciferase reporter assay. Moreover, the correlation between CRLF1 expression and miR-3065-3p was analyzed in colorectal cancer tissues. Finally, the effect of CRLF1 on the stemness and metastasis of colorectal cancer in vitro and in vivo was assessed.Results: In this report, we found that miR-3065-3p was overexpressed in colorectal cancer and that its high expression was associated with poor prognosis of patients with colorectal cancer. miR-3065-3p promotes the stemness and metastasis of colorectal cancer. Furthermore, CRLF1 was the downstream target of miR-3065-3p and inhibited the stemness of colorectal cancer. In addition, CRLF1 expression was negatively correlated with miR-3065-3p in colorectal cancer tissues. And, CRLF1 mediated the effects of miR-3065-3p on promoting stemness of colorectal cancer cells.Conclusion: Our data suggest that miR-3065-3p promoted the stemness and metastasis of colorectal cancer by targeting CRLF1. miR-3065-3p might serve as a promising prognostic marker as well as a therapeutic target for colorectal cancer. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs) are closely associated with the occurrences and progress of gastric cancer (GC). We aimed to delve into the function and pathological mechanism of Circular RNA-0002570 (circ-0002570) in GC progression. Methods: CircRNAs differentially expressed in GC were screened using bioinformatics technology. The expression of circ-0002570 was detected in GC specimens and cells via qRT-PCR, and the prognostic values of circ-0002570 were determined. The functional roles of circ-0002570 on proliferation, migration, and invasion in GC cells were explored in vitro and in vivo. Interaction of circ-0002570, miR-587, and VCAN was confirmed by dual-luciferase reporter assays, Western blotting, and rescue experiments. Results: Circ-0002570 expression was distinctly increased in GC tissues compared to adjacent normal specimens, and GC patients with higher circ-0002570 expressions displayed a short survival. Functionally, knockdown of circ-0002570 resulted in the inhibition of cell proliferation, migration, and invasion, and suppressed tumor growth in vivo. Mechanistically, miR-587 was sponged by circ-0002570. VCAN expression in NSCLC was directly inhibited by miR-587. Overexpression of circ-0002570 prevented VCAN from miR-587-mediated degradation and thus facilitated GC progression. Conclusion: The circ-0002570-miR-587-VCAN regulatory pathway promoted the progression of GC. Our findings provided potential new targets for the diagnosis and therapy of GC. [ABSTRACT FROM AUTHOR]

Introduction: MiRNAs play a critical role in carcinogenesis, among which miR-10a-5p has been reported in several types of human cancer. Nevertheless, the role of miR-10a-5p remain uncovered in bladder cancer (BCa). Methods: We recruited 88 BCa patients and 36 healthy controls (HC) to form the training cohort, and other 120 BCa patients to form the validation cohort. The clinical samples were collected for analysis. The expression level of miR-10a-5p was evaluated using RT-qPCR. Receiver operating characteristic (ROC) curves were utilized to calculate diagnostic accuracy. Survival curves were generated to analyze survival outcomes. CCK-8 and transwell assays were conducted to test the cell proliferation, migration, and invasion capacities. Results: MiR-10a-5p was upregulated in human BCa tissues and closely associated with advanced clinicopathological features, including advanced tumor grade, histological grade, and T stage. High expression of miR-10a-5p was associated with worse survival outcomes in BCa patients. Circulating plasma miR-10a-5p expression had the great performance power to discriminate BCa patients form HC patients before surgery, and to differentiate muscle invasive bladder cancer (MIBC) from non-muscle invasive bladder cancer (NMIBC). In addition, overexpression of miR-10a-5p could promote BCa cell proliferation, migration, and invasion. Conclusion: This study indicates that miR-10a-5p is a crucial diagnostic and prognostic biomarker for BCa patients, and miR-10a-5p exerted a tumor promoting role during BCa cell progression. [ABSTRACT FROM AUTHOR]

Background: Brain metastases were rare in esophageal cancer patients. Using the Surveillance, Epidemiology, and End Results (SEER) database, the present study investigated the incidence, risk and prognostic factors of brain metastases in esophageal cancer patients.Methods: Retrieving esophageal cancer patients diagnosed between 2010 and 2018 from the SEER database, univariable and multivariable logistic and cox regression models were used to investigate the risk factors for brain metastases development and prognosis, respectively. The brain metastases predicting nomogram was constructed, evaluated and validated. The overall survival (OS) of patients with brain metastases was analyzed by Kaplan-Meier method.Results: A total of 34,107 eligible esophageal cancer patients were included and 618 of them were diagnosed with brain metastases (1.8%). The median survival of the brain metastatic esophageal cancer patients was 5 (95% CI: 5-7) months. The presence of bone metastases and lung metastases were the homogeneously associated factors for the development and prognosis of brain metastases in esophageal cancer patients. Patients younger than 65 years, American Indian/Alaska Native race (vs. White), overlapping lesion (vs. Upper third), esophageal adenocarcinoma histology subtype, higher N stage, and liver metastases were positively associated with brain metastases occurrence. The calibration curve, ROC curve, and C-index exhibited good performance of the nomogram for predicting brain metastases.Conclusions: Homogeneous and heterogeneous factors were found for the development and prognosis of brain metastases in esophageal cancer patients. The nomogram had good calibration and discrimination for predicting brain metastases. [ABSTRACT FROM AUTHOR]

Background: Due to the rarity of adenosquamous carcinoma of the cervix (ASCC), studies on the incidence, prognostic factors, and treatment outcomes of ASCC remain scarce. Therefore, we performed a retrospective population-based study to systematically investigate the characteristics of ASCC patients. Methods: Patients with a histopathologically confirmed diagnosis of ASCC were enrolled from the Surveillance, Epidemiology, and End Results database between 1975 and 2016. Univariate and multivariate Cox regression analyses were performed to identify the potential predictors of cancer-specific survival (CSS) in patients with ASCC. Selected variables were integrated to establish a predictive nomogram and the predictive performance of the nomogram was estimated using Harrell's concordance index (C-index), calibration curve, and decision curve analysis (DCA). Results: A total of 1142 ASCC patients were identified and included in this study and were further randomized into the training and validation cohorts in a 7:3 ratio. The age-adjusted incidence of ASCC declined from 0.19 to 0.09 cases per 100,000 person-years between 2000 and 2017, with an annual percentage change of -4.05% (P<0.05). We identified age, tumor grade, FIGO stage, tumor size, and surgical procedure as independent predictors for CSS in ASCC patients and constructed a nomogram to predict the 3- and 5-year CSS using these prognostic factors. The calibration curve indicated an outstanding consistency between the nomogram prediction and actual observation in both the training and testing cohorts. The C-index was 0.7916 (95% CI: 0.7990-0.8042) and 0.8148 (95% CI: 0.7954-0.8342) for the training and testing cohorts, respectively, indicating an excellent discrimination ability of the nomogram. The DCA showed that the nomogram exhibited more clinical benefits than the FIGO staging system. Conclusions: We established and validated an accurate predictive nomogram for ASCC patients based on several clinical characteristics. This model might serve as a useful tool for clinicians to estimate the prognosis of ASCC patients. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the most common types of cancers and the leading cause of death from malignancy among women worldwide. Tumor-infiltrating lymphocytes are a source of important prognostic biomarkers for breast cancer patients. In this study, based on the tumor-infiltrating lymphocytes in the tumor immune microenvironment, a risk score prognostic model was developed in the training cohort for risk stratification and prognosis prediction in breast cancer patients. The prognostic value of this risk score prognostic model was also verified in the two testing cohorts and the TCGA pan cancer cohort. Nomograms were also established in the training and testing cohorts to validate the clinical use of this model. Relationships between the risk score, intrinsic molecular subtypes, immune checkpoints, tumor-infiltrating immune cell abundances and the response to chemotherapy and immunotherapy were also evaluated. Based on these results, we can conclude that this risk score model could serve as a robust prognostic biomarker, provide therapeutic benefits for the development of novel chemotherapy and immunotherapy, and may be helpful for clinical decision making in breast cancer patients. [ABSTRACT FROM AUTHOR]

Background: We investigated if the concentration and "rangeability" of cystatin C (CysC) influenced the prognosis of coronavirus disease 2019 (COVID-19) in patients suffering from, or not suffering from, type 2 diabetes mellitus (T2DM). Methods: A total of 675 T2DM patients and 572 non-T2DM patients were divided into "low" and "high" CysC groups and low and high CysC-rangeability groups according to serum CysC level and range of change of CysC level, respectively. Demographic characteristics, clinical data, and laboratory results of the four groups were analyzed. Results: COVID-19 patients with a high level and rangeability of CysC had more organ damage and a higher risk of death compared with those with a low level or low rangeability of CysC. Patients with a higher level and rangeability of CysC had more blood lymphocytes and higher levels of C-reactive protein, alanine aminotransferase, and aspartate aminotransferase. After adjustment for possible confounders, multivariate analysis revealed that CysC >0.93 mg/dL was significantly associated with the risk of heart failure (OR = 2.231, 95% CI: 1.125–5.312) and all-cause death (2.694, 1.161–6.252). CysC rangeability >0 was significantly associated with all-cause death (OR = 4.217, 95% CI: 1.953–9.106). These associations were stronger in patients suffering from T2DM than in those not suffering from T2DM. Conclusions: The level and rangeability of CysC may influence the prognosis of COVID-19. Special care and appropriate intervention should be undertaken in COVID-19 patients with an increased CysC level during hospitalization and follow-up, especially for those with T2DM. [ABSTRACT FROM AUTHOR]

Germline copy number variant (gCNV) has been studied as a genetic determinant for prognosis of several types of cancer, but little is known about how it affects non-small cell lung cancer (NSCLC) prognosis. We aimed to develop a prognostic nomogram for NSCLC based on gCNVs. Promising gCNVs that are associated with overall survival (OS) of NSCLC were sorted by analyzing the TCGA data and were validated in a small Chinese population. Then the successfully verified gCNVs were determined in a training cohort (n = 570) to develop a prognostic nomogram, and in a validation cohort (n = 465) to validate the nomogram. Thirty-five OS-related gCNVs were sorted and were reduced to 15 predictors by the Lasso regression analysis. Of them, only CNVR395.1 and CNVR2239.1 were confirmed to be associated with OS of NSCLC in the Chinese population. High polygenic risk score (PRS), which was calculated by the hazard effects of CNVR395.1 and CNVR2239.1, exerted a significantly higher death rate in the training cohort (HR = 1.41, 95%CI: 1.16–1.74) and validation cohort (HR = 1.42, 95%CI: 1.13–1.77) than low PRS. The nomogram incorporating PRS and surrounding factors, achieved admissible concordance indexes of 0.678 (95%CI: 0.664–0.693) and 0.686 (95%CI: 0.670–0.702) in predicting OS in the training and validation cohorts, respectively, and had well-fitted calibration curves. Moreover, an interaction between PRS and asbestos exposure was observed on affecting OS (P interaction = 0.042). Our analysis developed a nomogram that achieved an admissible prediction of NSCLC survival, which would be beneficial to the personalized intervention of NSCLC. [ABSTRACT FROM AUTHOR]

A non-invasive method to distinguish potential lung cancer patients would improve lung cancer prevention. We employed the RNA-sequencing analysis to profile serum exosomal long non-coding RNAs (lncRNAs) from non-small cell lung cancer (NSCLC) patients and pneumonia controls, and then determined the diagnostic and prognostic value of a promising lncRNA in four datasets. We identified 90 dysregulated lncRNAs for NSCLC and found the most significant lncRNA was a novel isoform of linc01125. Serum exosomal linc01125 could distinguish NSCLC cases from disease-free and tuberculosis controls, with the area under the curve values as 0.662 [95% confidence interval (CI) = 0.614–0.711] and 0.624 (95% CI = 0.522–0.725), respectively. High expression of exosomal linc01125 was also correlated with an unfavorable overall survival of NSCLC (hazard ratio = 1.48, 95% CI = 1.05–2.08). Clinic treatment decreased serum exosomal linc01125 in NSCLC patients (P = 0.036). Linc01125 functions to inhibit cancer growth and metastasis via acting as a competing endogenous RNA to up-regulate tumor necrosis factor alpha-induced protein 3 (TNFAIP3) expression by sponging miR-19b-3p. Notably, the oncogenic transformation of 16HBE led to decreased linc01125 in cells but increased linc01125 in cell-derived exosomes. The expression of linc01125 in total exosomes was highly correlated with that in tumor-associated exosomes in serum. Moreover, lung cancer cells were capable of releasing linc01125 into exosomes in vitro and in vivo. Our analyses suggest serum exosomal linc01125 as a promising biomarker for non-invasively diagnosing NSCLC and predicting the prognosis of NSCLC. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the most human malignant diseases and the leading cause of cancer-related death in the world. However, the prognostic and therapeutic benefits of breast cancer patients cannot be predicted accurately by the current stratifying system. In this study, an immune-related prognostic score was established in 22 breast cancer cohorts with a total of 6415 samples. An extensive immunogenomic analysis was conducted to explore the relationships between immune score, prognostic significance, infiltrating immune cells, cancer genotypes and potential immune escape mechanisms. Our analysis revealed that this immune score was a promising biomarker for estimating overall survival in breast cancer. This immune score was associated with important immunophenotypic factors, such as immune escape and mutation load. Further analysis revealed that patients with high immune scores exhibited therapeutic benefits from chemotherapy and immunotherapy. Based on these results, we can conclude that this immune score may be a useful tool for overall survival prediction and treatment guidance for patients with breast cancer. [ABSTRACT FROM AUTHOR]

This study focused on the expression of mitochondrial serine hydroxymethyltransferase (SHMT2) in oral squamous cell carcinoma (OSCC) and its correlation with clinical traits and the prognosis of OSCC patients. Immunochemical staining and Western blotting were used to quantify the expression of SHMT2 and related immune markers in OSCC. Using OSCC microarrays and The Cancer Genome Atlas (TCGA) database, we evaluated the association between SHMT2 and various clinical traits. We found that increased expression of SHMT2 was detected in OSCC and correlated with advanced pathological grade and recurrence of OSCC. By a multivariate Cox proportional hazard model, high expression of SHMT2 was shown to indicate a negative prognosis. In addition, in the OSCC microenvironment, increasing the expression of SHMT2 was associated with high expression levels of programmed cell death-ligand 1 (PD-L1), CKLF-like MARVEL transmembrane domain containing 6 (CMTM6), V-type immunoglobulin domain-containing suppressor (VISTA), B7-H4, Slug, and CD317. In the future, more effort will be required to investigate the role of SHMT2 in the OSCC microenvironment. [ABSTRACT FROM AUTHOR]

Background: Inflammation and nutrition are important causes contributing to the progression and poor survival of gastric cancer (GC). The objective of this study is to investigate the prognostic significance of the preoperative fibrinogen-to-pre-albumin ratio (FPR) and the prognostic nutritional index (PNI) in GC patients who have undergone gastrectomy. Methods: A total of 274 patients with resected pathological GC from January 2007 to December 2013 were enrolled in this retrospective study. Survival analysis was performed using Kaplan–Meier and log rank tests. Univariate and multivariate analyses were established to identify independent prognostic factors of 5-year survival. A predictive nomogram was used to predict prognosis of overall survival (OS), and its accuracy was determined by Harrell's concordance index (C index). Results: A high preoperative FPR-PNI score was significantly correlated with age, bigger tumor size, more lymphatic metastases and advanced TNM stage. Univariate analysis revealed that the GC patients with high FPR, low PNI and high FPR-PNI scores had shorter survival time. Multivariate analysis showed that FPR-PNI was an independent prognostic factor for OS in GC patients, especially in elderly patients. In the sub-analysis by age, the FPR-PNI score could significantly increase the accuracy of prognosis compared with the FPR and PNI alone in elderly GC patients. Conclusion: The preoperative FPR-PNI score is an effective independent prognostic index for GC patients after surgery, especially in elderly patients. [ABSTRACT FROM AUTHOR]

Lung squamous cell carcinoma (LSCC) is the most common subtype of non-small cell lung cancer. Immunotherapy has become an effective treatment in recent years, while patients showed different responses to the current treatment. It is vital to identify the potential immunogenomic signatures to predict patient' prognosis. The expression profiles of LSCC patients with the clinical information were downloaded from TCGA database. Differentially expressed immune-related genes (IRGs) were extracted using edgeR algorithm, and functional enrichment analysis showed that these IRGs were primarily enriched in inflammatory- and immune-related processes. "Cytokine-cytokine receptor interaction" and "PI3K-AKT signaling pathway" were the most enriched KEGG pathways. 27 differentially expressed IRGs were significantly correlated with the overall survival (OS) of patients using univariate Cox regression analysis. A prognostic risk signature that comprises seven IRGs (GCCR, FGF8, CLEC4M, PTH, SLC10A2, NPPC, and FGF4) was developed with effective predictive performance by multivariable Cox stepwise regression analysis. Most importantly, the signature could be an independent prognostic predictor after adjusting for clinicopathological parameters, and also validated in two independent LSCC cohorts (GSE4573 and GSE17710). Potential molecular mechanisms and tumor immune landscape of these IRGs were investigated through computational biology. Analysis of tumor infiltrating lymphocytes and immune checkpoint molecules revealed distinct immune landscape in high- and low-risk group. The study was the first time to construct IRG-based immune signature in the recognition of disease progression and prognosis of LSCC patients. [ABSTRACT FROM AUTHOR]

Background: The KIF5B-RET fusion gene is a novel oncogene that has been observed in a subset of lung cancers in recent years. However, the results of related epidemiological studies remain unclear. Thus, a meta-analysis was conducted to evaluate the correlation of KIF5B-RET expression based on RT-PCR detection with clinicopathological features and prognosis of lung cancer. Methods: The PubMed, Google Scholar, Wiley Online, SpringerLink and Chinese National Knowledge Infrastructure databases were searched to identify the eligible studies. The association of the occurrence of KIF5B-RET fusion gene in lung cancer with age, gender, smoking status, histology type, differentiation and TNM stage was analyzed. HR, overall survival (OS) and progression-free survival (PFS) were used to describe the prognosis of patients with lung cancer. The OR and 95% CI were calculated to assess the correlations. Random- and fixed-effects models were used to analyze the data. Results: A total of 13 studies, which included 8,859 lung cancer patients, were included in the study based on the inclusion criteria. A total of 121 patients with positive KIF5B-RET fusion gene status were detected, with a positive expression rate of 1.36%. KIF5B-RET fusion gene status was identified at significantly higher frequencies in female (OR=0.67, 95% CI=0.48–0.94) than male patients, and the same trend was found in young (<60 years) patients (OR=0.08, 95% CI=0.01–0.45) compared with old patients (≥60 years). No differences were found in the TNM stage, histology, differentiation and smoking. Based on the prognosis, no difference was found between the status of the positive and negative KIF5B-RET fusion genes in OS and PFS of patients. Conclusion: The KIF5B-RET fusion gene occurred predominantly in young female patients with lung cancer. However, the relationship between the expression of the fusion gene and the prognosis of lung patients remains unclear. [ABSTRACT FROM AUTHOR]

Gastric cancer is one of the most common types of malignancy worldwide. However, the molecular mechanisms of cancer development remain unclear. Src-associated in mitosis of 68 kDa (Sam68) is involved in cell proliferation, transformation, tumorigenesis and metastasis in several types of cancer. The present study aimed to assess the expression and function of Sam68 in human gastric cancer. Western blot analysis and immunohistochemistry indicated that Sam68 expression was increased in tumor samples and the levels were associated with the grade of malignancy. High Sam68 expression was associated with the poor prognosis of patients with gastric cancer. In vitro, following knockdown of Sam68 by transfection of gastric cancer cells with small interfering RNA, the cell viability, cell cycle progress, migration and invasion were decreased. The results of the present study revealed that Sam68 may be a novel prognostic factor for, and is associated with cell growth, migration and invasion in, gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Whether there are differences in pathogenesis among different types and subtypes of cerebral watershed infarction (WSI) is controversial since they have been combined into a single group in most previous studies.Methods: We prospectively identified 340 supratentorial WSI patients at Beijing Chao-Yang Hospital, Capital Medical University, China and classified them based on diffusion-weighted imaging(DWI) templates. Baseline characteristics, clinical courses and neuroradiological features were compared among patients with different types and subtypes of WSI.Results: We identified 92 patients with cortical watershed infarction (CWI), 112 with internal watershed infarction (IWI) and 136 with mixed-type infarction. Compared with CWI patients, more IWI patients had critical stenosis of internal carotid artery (ICA) (P < 0.001). For the CWI group, patients with anterior watershed infarction (AWI) were more prone to critical ICA stenosis than those with posterior watershed infarction (PWI) (P = 0.011). For the IWI group, critical ICA stenosis was more prevalent in patients with partial IWI (P-IWI) than in those with confluent IWI (C-IWI) (P = 0.026). IWI patients were more frequently found to have clinical deterioration during the first 7 days of hospitalization and a poor prognosis at the 90th day than in CWI patients (P = 0.003 and P = 0.014, respectively).Conclusions: IWI, especially the P-IWI subtype, is associated with hemodynamic impairment (HDI), whereas CWI has a weaker correlation with ICA steno-occlusion. Furthermore, IWI patients are more prone to poor prognosis. [ABSTRACT FROM AUTHOR]

Promoter hypermethylation-mediated inactivation of ID4 plays a crucial role in the development of solid tumours. This study aimed to investigate ID4 methylation and its clinical relevance in myeloid malignancies. ID4 hypermethylation was associated with higher IPSS scores, but was not an independent prognostic biomarker affecting overall survival (OS) in myelodysplastic syndrome (MDS). However, ID4 hypermethylation correlated with shorter OS and leukaemia-free survival (LFS) time and acted as an independent risk factor affecting OS in acute myeloid leukaemia (AML). Moreover, ID4 methylation was significantly decreased in the follow-up paired AML patients who achieved complete remission (CR) after induction therapy. Importantly, ID4 methylation was increased during MDS progression to AML and chronic phase (CP) progression to blast crisis (BC) in chronic myeloid leukaemia (CML). Epigenetic studies showed that ID4 methylation might be one of the mechanisms silencing ID4 expression in myeloid leukaemia. Functional studies in vitro showed that restoration of ID4 expression could inhibit cell proliferation and promote apoptosis in both K562 and HL60 cells. These findings indicate that ID4 acts as a tumour suppressor in myeloid malignancies, and ID4 methylation is a potential biomarker in predicting disease progression and treatment outcome. [ABSTRACT FROM AUTHOR]

Background: Mild encephalitis/encephalopathy with reversible splenial lesion (MERS) is a rare clinico-radiological entity characterized by the magnetic resonance imaging (MRI) finding of a reversible lesion in the corpus callosum, sometimes involved the symmetrical white matters. Many cases of child-onset MERS with various causes have been reported. However, adult-onset MERS is relatively rare. The clinical characteristics and pathophysiologiccal mechanisms of adult-onset MERS are not well understood. We reviewed the literature on adult-onset MERS in order to describe the characteristics of MERS in adults and to provide experiences for clinician.Methods: We reported a case of adult-onset MERS with acute urinary retension and performed literature search from PubMed and web of science databases to identify other adult-onset MERS reports from Januarary 2004 to March 2016. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed on selection process. And then we summarized the clinico-radiological features of adult-onset MERS.Results: Twenty-nine adult-onset MERS cases were reviewed from available literature including the case we have. 86.2% of the cases (25/29) were reported in Asia, especially in Japan. Ages varied between 18 and 59 years old with a 12:17 female-to-male ratio. The major cause was infection by virus or bacteria. Fever and headache were the most common clinical manifestation, and acute urinary retention was observed in 6 patients. All patients recovered completely within a month.Conclusion: Adult-onset MERS is an entity with a broad clinico-radiological spectrum because of the various diseases and conditions. There are similar characteristics between MERS in adults and children, also some differences. [ABSTRACT FROM AUTHOR]

Epigenetic inactivation of GPX3 has been identified in various cancers including leukemia. Moreover, aberrant DNA methylation was also found as a dominant mechanism of disease progression in myelodysplastic syndrome ( MDS). This study intended to explore GPX3 promoter methylation and its clinical relevance in 110 patients with MDS. GPX3 methylation was examined by real-time quantitative methylation-specific PCR ( RQ- MSP) and bisulfite sequencing PCR ( BSP). GPX3 methylation was identified in 15% (17/110) MDS patients, and significantly higher than controls, and lower than acute myeloid leukemia ( AML) patients ( P = 0.024 and 0.041). GPX3 methylated patients had older age and higher frequency of DNMT3A mutation ( P = 0.015 and 0.066). Cases with GPX3 methylation showed significantly shorter overall survival ( OS) time than those with GPX3 unmethylation analyzed with Kaplan-Meier analysis ( P = 0.012). Moreover, Cox regression analysis revealed that GPX3 methylation might act as an independent prognostic indicator in MDS ( HR = 1.847, P = 0.072). GPX3 methylation density was significantly increased during the progression from MDS to secondary acute myeloid leukemia ( sAML) in three follow-up paired patients. Our study concludes that GPX3 methylation in bone marrow is associated with adverse prognosis and leukemia transformation in MDS. [ABSTRACT FROM AUTHOR]

Transcription factors directly bind to DNA and regulate the expression of the gene, causing epigenetic modification of the DNA. They often mediate epigenetic parameters of transcriptional and posttranscriptional mechanisms, and their expression activities can be used to characterize genomic aberrations in cancer cell. In this study, the activity profile of transcription factors inferred by VIPER algorithm. The autoencoder model was applied for compressing the transcription factor activity profile for obtaining more useful transformed features for stratifying patients into two different breast cancer subtypes. The deep learning-based subtypes exhibited superior prognostic value and yielded better risk-stratification than the transcription factor activity-based method. Importantly, according to transformed features, a deep neural network was constructed to predict the subtypes, and achieved the accuracy of 94.98% and area under the ROC curve of 0.9663, respectively. The proposed subtypes were found to be significantly associated with immune infiltration, tumor immunogenicity and so on. Furthermore, the ceRNA network was constructed for the breast cancer subtypes. Besides, 11 master regulators were found to be associated with patients in cluster 1. Given the robustness performance of our deep learning model over multiple breast cancer cohorts, we expected this model may be useful in the area of prognosis prediction and lead some possibility for personalized medicine in breast cancer patients. • The autoencoder was used for compressing the transcription factor activity profile. • This model illustrated better predictive accuracy and prognosis outcome. • This stratification was significantly associated with genomic landscape. [ABSTRACT FROM AUTHOR]

Recent genome-wide association studies implicated that the nicotinic acetylcholine receptors (nAChRs) are common susceptible genes of two contextual diseases: chronic obstructive pulmonary disease (COPD) and lung cancer. We aimed to test whether the copy number variations (CNVs) in nAChRs have hereditary contributions to development of the two diseases. In two, two-stage, case-control studies of southern and eastern Chinese, a common CNV-3956 that duplicates the cholinergic receptor, nicotinic, α7 (CHRNA7) gene was genotyped in a total of 7880 subjects and its biological phenotype was assessed. The ≥4-copy of CNV-3956 increased COPD risk (≥4-copy vs 2/3-copy: OR=1.44, 95% CI=1.23-1.68) and caused poor lung function, and it similarly augmented risk (OR=1.49, 95% CI=1.29-1.73) and worsened prognosis (hazard ratio (HR)=1.25, 95% CI=1.07-1.45) of lung cancer. The ≥4-copy was estimated to account for 1.56% of COPD heritability and 1.87% of lung cancer heritability, respectively. Phenotypic analysis further showed that the ≥4-copy of CNV-3956 improved CHRNA7 expression in vivo and increased the carriers' smoking amount. The CNV-3956 of CHRNA7 contributed to increased risks and poor prognoses of both COPD and lung cancer, and this may be a genetic biomarker of the two diseases. [ABSTRACT FROM AUTHOR]

Hotspot mutations of serine/arginine-rich splicing factor 2 (SRSF2) gene have been identified in a proportion of hematologic malignancies including myelodysplastic syndrome (MDS). The aim of the present study was to develop a new approach to screen SRSF2 mutation and analyze the clinical relevance of SRSF2 mutations in Chinese MDS. A protocol based on high-resolution melting analysis (HRMA) was established to screen SRSF2-P95 mutation in 108 MDS patients and was compared with Sanger sequencing. The clinical relevance of SRSF2 mutations was further evaluated. HRMA identified five (4.6%) cases with SRSF2 mutation, completely validated by Sanger sequencing without false positive or negative results. The sensitivities of HRMA and Sanger sequencing were 10% and 25% for the detection of SRSF2-P95H mutation, respectively, against the background of wild-type DNA. Patients with SRSF2 mutation had shorter overall survival time than those with wild-type SRSF2 in both the whole cohort of cases and those with normal karyotype (P = 0.069 and 0.023, respectively). Multivariate analysis confirmed SRSF2 mutation as an independent risk factor in both patient populations. We established a fast, high-throughput, and inexpensive HRMA-based method to screen SRSF2 mutation, which could be used in clinical diagnostic laboratories. SRSF2 mutations were significantly associated with mortality rate in the MDS affected Chinese. [ABSTRACT FROM AUTHOR]

• A OS-related signature with robust predictive performance was developed based on proteomic profile of SARC patients from TPCA database. • The signature was validated from transcriptomic dataset of SARC patients from TCGA, and could be independent prognostic predictor after adjusting for clinicopathological parameters. • The signature has predictive capacity for predicting progression free intervals and disease free intervals for SARC patients. • Tumor infiltrating lymphocytes and immune checkpoint molecules analysis revealed distinctly immune landscapes of high- and low-risk patients. Sarcoma (SARC) represents a group of highly histological and molecular heterogeneous rare malignant tumors with poor prognosis. There are few proposed classifiers for predicting patient's outcome. The Cancer Proteome Atlas (TPCA) and The Cancer Genome Atlas (TCGA) databases provide multi-omics datasets that enable a comprehensive investigation for this disease. The proteomic expression profile of SARC patients along with the clinical information was downloaded. 55 proteins were found to be associated with overall survival (OS) of patients using univariate Cox regression analysis. We developed a prognostic risk signature that comprises seven proteins (AMPKALPHA, CHK1, S6, ARID1A, RBM15, ACETYLATUBULINLYS40, and MSH6) with robust predictive performance using multivariate Cox stepwise regression analysis. Additionally, the signature could be an independent prognostic predictor after adjusting for clinicopathological parameters. Patients in high-risk group also have worse progression free intervals (PFI) than that of patients in low-risk group, but not for disease free intervals (DFI). The signature was validated using transcriptomic profile of SARC patients from TCGA. Potential mechanisms between high- and low-risk groups were identified using differentially expressed genes (DEGs) analysis. These DEGs were primarily enriched in RAS and MPAK signaling pathways. The signature protein molecules are candidate biomarkers for SARC, and the analysis of computational biology in tumor infiltrating lymphocytes and immune checkpoint molecules revealed distinctly immune landscapes of high- and low-risk patients. Together, we constructed a prognostic signature for predicting outcomes for SARC integrating proteomic and transcriptomic profiles, this might have value in guiding clinical practice. [ABSTRACT FROM AUTHOR]

• RNAscope in situ hybridization was used to determine FAM83H-AS1 expression. • FAM83H-AS1 was significantly higher in cancer tissues than in paired normal mucosa from colon cancer patients. • High levels of FAM83H-AS1 predicts a poor prognosis in the patients with colon cancer. • FAM83H-AS1 downregulation promoted SMAD1 expression. Long noncoding RNAs (LncRNAs) have been proven to participate in many principal pathways during colonic mucosa tumourigenesis. FAM83H-AS1 has been identified as one of the LncRNAs that is dysregulated in multi-type cancers. Here, our purpose was to determine the expression pattern and clinical significance of FAM83H-AS1 and further analyse its prognostic value in colon cancer. FAM83H-AS1 expression was examined in 90 patients with colon cancer by RNAscope in situ hybridization, and the expression levels were analysed with the overall survival (OS) rates for patients with colon cancer. TCGA datasets derived from colon cancer (COAD) were used to further validate the main findings. We demonstrated that the expression of FAM83H-AS1 was significantly higher in cancer tissues than in paired normal mucosa from colon cancer patients (P < 0.001). The prognostic analysis indicated that the OS rates for colon cancer patients with high levels of FAM83H-AS1 were significantly lower than those for patients with low levels of FAM83H-AS1 (P = 0.013). The higher levels of FAM83H-AS1 were found to be associated with a lower expression of SMAD1/5/9, which is involved in TGF-β signalling in colon cancer tissues (P = 0.0174). In HCT116 and SW480 cell lines, the down regulation of FAM83H-AS1 promoted the expression of SMAD1. Our investigations suggest that the upregulation of FAM83H-AS1 serves as a promising predictor and might be conducive for clinicians to estimate OS time. FAM83H-AS1 might serve as an inhibitor of TGF-β signalling. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) represent a novel class of non-coding RNAs that play significant roles in tumorigenesis and tumor progression. High-throughput sequencing of gastric cancer (GC) tissues has identified circRNA BIRC6 (circBIRC6) as a potential circRNA derived from the BIRC6 gene, exhibiting significant upregulation in GC tissues. The expression of circBIRC6 is notably elevated in GC patients. Functionally, it acts as a molecular sponge for miR-488, consequently upregulating GRIN2D expression and promoting GC proliferation, migration, and invasion. Moreover, overexpression of circBIRC6 leads to increased GRIN2D expression, which in turn enhances caveolin-1 (CAV1) expression, resulting in autophagy deficiency due to miR-488 sequestration. This cascade of events significantly influences tumorigenesis in vivo. Our findings collectively illustrate that the CircBIRC6-miR-488-GRIN2D axis fosters CAV1 expression in GC cells, thereby reducing autophagy levels. Both circBIRC6 and GRIN2D emerge as potential targets for treatment and independent prognostic factors for GC patients. [Display omitted] [ABSTRACT FROM AUTHOR]