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J Cancer 2020; 11(10):3027-3040. doi:10.7150/jca.40866 This issue Cite

Research Paper

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

Kelei Guan^1†, Xin Liu^2†, Jianhao Li^2†, Yanxia Ding³, Juan Li², Guangying Cui², Xichun Cui^3✉, Ranran Sun^2✉

1. Department of pharmacy, the First Affiliated Hospital of Zhengzhou University
2. Precision Medicine Center, the First Affiliated Hospital of Zhengzhou University
3. Key Laboratory of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University
† These authors contributed equally to this work.
✉ Corresponding author: Ranran Sun, Precision Medicine Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. Tel & Fax: +86-371-67966905. E-mail address: fccsunrr@zzu.edu.cn; Xichun Cui, Key Laboratory of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. Tel & Fax: +86-371-67966905. E-mail address: xichun639@163.com

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.

Keywords: gastric cancer, N6-methyladenosine, prognostic, WTAP, FTO.

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