Dataset Information

Expression Status And Prognostic Value Of M6A-associated Genes in Gastric Cancer.

ABSTRACT: Purpose: Gastric cancer (GC) is a primary cause of cancer-associated mortality worldwide. N6-methyladenosine (m6A) is one of the most common RNA modifications that involves in the progression of numerous cancers. However, the expression status and function of m6A-related genes in gastric cancer is still not well understood. The current study is aimed to investigate the expression status and determinate prognostic value of m6A-related genes in gastric cancer. Methods: m6A-asssociated gene expression was evaluated via analyzing the expression data of GC patients from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. The protein expression levels of m6A-associated molecules were further validated by immunohistochemical (IHC) staining data from GC tissue microarray (TMA) cohort and Human Protein Atlas (HPA) database. Kaplan-Meier analysis was performed to assess the prognostic value of m6A-associated genes in gastric cancer. Risk score model was established by lasso COX regression analysis and its prognostic predicted efficiency was assessed by the receiver-operator characteristic (ROC) curve. Cox regression analyses were used for exploring risk factors related to GC patient prognosis. Results: Most of m6A-related genes were upregulated at both mRNA and protein levels in gastric cancer tissues compared with that in normal gastric tissues. The expression levels of m6A-related genes were associated with clinicopathological features including race, age and TNM stage. High expression of WTAP and FTO predicted poor prognosis of GC patients. Survival analysis demonstrated that patients with high-risk scores had worse overall survival (OS) and ROC curves suggested the prediction performance for gastric patients. Moreover, Cox regression analyses indicated that m6A risk model score was a prognostic factor for OS and FTO upregulation might be a potential independent prognostic factor for recurrence-free survival (RFS) in gastric cancer patients. Conclusion: m6A-related genes were dysregulated in GC and were closely associated with prognosis of GC patients. FTO might serve as a novel prognostic biomarker for gastric cancer, while the m6A-related risk score might be informative for risk assessment and prognostic stratification.

SUBMITTER: Guan K

PROVIDER: S-EPMC7086255 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Expression Status And Prognostic Value Of M6A-associated Genes in Gastric Cancer.

Guan Kelei K Liu Xin X Li Jianhao J Ding Yanxia Y Li Juan J Cui Guangying G Cui Xichun X Sun Ranran R

Journal of Cancer 20200304 10

<b>Purpose</b>: Gastric cancer (GC) is a primary cause of cancer-associated mortality worldwide. N6-methyladenosine (m6A) is one of the most common RNA modifications that involves in the progression of numerous cancers. However, the expression status and function of m6A-related genes in gastric cancer is still not well understood. The current study is aimed to investigate the expression status and determinate prognostic value of m6A-related genes in gastric cancer. <b>Methods</b>: m6A-asssociate ...[more]

PMID: 32226518

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Project description:Previous studies have reported that alcohol dehydrogenase (ADH) isoenzymes possess diagnostic value in gastric cancer (GC). However, the prognostic value of ADH isoenzymes in GC remains unclear. The aim of the present study was to identify the prognostic value of ADH genes in patients with GC. The prognostic value of ADH genes was investigated in patients with GC using the Kaplan-Meier plotter tool. Kaplan-Meier plots were used to assess the difference between groups of patients with GC with different prognoses. Hazard ratios (HR) and 95% confidence intervals (CI) were used to assess the relative risk of GC survival. Overall, 593 patients with GC and 7 ADH genes were included in the survival analysis. High expression of ADH 1A (class 1), ? polypeptide (ADH1A; log-rank P=0.043; HR=0.79; 95% CI: 0.64-0.99), ADH 1B (class 1), ? polypeptide (ADH1B; log-rank P=1.9×10-05; HR=0.65; 95% CI: 0.53-0.79) and ADH 5 (class III), ? polypeptide (ADH5; log-rank P=0.0011; HR=0.73; 95% CI: 0.6-0.88) resulted in a significantly decreased risk of mortality in all patients with GC compared with patients with low expression of those genes. Furthermore, protective effects may additionally be observed in patients with intestinal-type GC with high expression of ADH1B (log-rank P=0.031; HR=0.64; 95% CI: 0.43-0.96) and patients with diffuse-type GC with high expression of ADH1A (log-rank P=0.014; HR=0.51; 95% CI: 0.3-0.88), ADH1B (log-rank P=0.04; HR=0.53; 95% CI: 0.29-0.98), ADH 4 (class II), ? polypeptide (log-rank P=0.033; HR=0.58; 95% CI: 0.35-0.96) and ADH 6 (class V) (log-rank P=0.037; HR=0.59; 95% CI: 0.35-0.97) resulting in a significantly decreased risk of mortality compared with patients with low expression of those genes. In contrast, patients with diffuse-type GC with high expression of ADH5 (log-rank P=0.044; HR=1.66; 95% CI: 1.01-2.74) were significantly correlated with a poor prognosis. The results of the present study suggest that ADH1A and ADH1B may be potential prognostic biomarkers of GC, whereas the prognostic value of other ADH genes requires further investigation.

Project description:Background: Gastric cancer (GC) is a digestive system tumor with high morbidity and mortality rates. Molecular targeted therapies, including those targeting human epidermal factor receptor 2 (HER2), have proven to be effective in clinical treatment. However, better identification and description of tumor-promoting genes in GC is still necessary for antitumor therapy. Methods: Gene expression and clinical data of GC patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Last absolute shrinkage and selection operator (LASSO) Cox regression were applied to build a prognostic model, the Prognosis Score. Functional enrichment and single-sample gene set enrichment analysis (ssGSEA) were used to explore potential mechanisms. Western blotting, RNA interference, cell migration, and wound healing assays were used to detect the expression and function of myosin light chain 9 (MYL9) in GC. Results: A four-gene prognostic model was constructed and GC patients from TCGA and meta-GEO cohorts were stratified into high-prognosis score groups or low-prognosis score groups. GC patients in the high-prognosis score group had significantly poorer overall survival (OS) than those in the low-prognosis score groups. The GC prognostic model was formulated as PrognosisScore = (0.06 × expression of BGN) - (0.008 × expression of ATP4A) + (0.12 × expression of MYL9) - (0.01 × expression of ALDH3A1). The prognosis score was identified as an independent predictor of OS. High expression of MYL9, the highest weighted gene in the prognosis score, was correlated with worse clinical outcomes. Functional analysis revealed that MYL9 is mainly associated with the biological function of epithelial-mesenchymal transition (EMT). Knockdown of MYL9 expression inhibits migration of GC cells in vitro. Conclusion: We found that PrognosisScore is potential reliable prognostic marker and verified that MYL9 promotes the migration and metastasis of GC cells.

Dataset Information

Expression Status And Prognostic Value Of M6A-associated Genes in Gastric Cancer.

Publications

Expression Status And Prognostic Value Of M6A-associated Genes in Gastric Cancer.

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