Guan Kelei, Liu Xin, Li Jianhao, Ding Yanxia, Li Juan, Cui Guangying, Cui Xichun, Sun Ranran
Department of pharmacy, the First Affiliated Hospital of Zhengzhou University.
Precision Medicine Center, the First Affiliated Hospital of Zhengzhou University.
J Cancer. 2020 Mar 4;11(10):3027-3040. doi: 10.7150/jca.40866. eCollection 2020.
: 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. : 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. : 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. : 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.
胃癌(GC)是全球癌症相关死亡的主要原因之一。N6-甲基腺苷(m6A)是最常见的RNA修饰之一,参与多种癌症的进展。然而,m6A相关基因在胃癌中的表达状态和功能仍未完全明确。本研究旨在调查m6A相关基因在胃癌中的表达状态并确定其预后价值。:通过分析来自癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)的GC患者的表达数据,评估m6A相关基因的表达。m6A相关分子的蛋白质表达水平通过来自GC组织芯片(TMA)队列和人类蛋白质图谱(HPA)数据库的免疫组织化学(IHC)染色数据进一步验证。进行Kaplan-Meier分析以评估m6A相关基因在胃癌中的预后价值。通过套索COX回归分析建立风险评分模型,并通过受试者工作特征(ROC)曲线评估其预后预测效率。使用COX回归分析探索与GC患者预后相关的危险因素。:与正常胃组织相比,大多数m6A相关基因在胃癌组织中的mRNA和蛋白质水平均上调。m6A相关基因的表达水平与包括种族、年龄和TNM分期在内的临床病理特征相关。WTAP和FTO的高表达预示着GC患者预后不良。生存分析表明,高风险评分的患者总生存期(OS)较差,ROC曲线显示了对胃癌患者的预测性能。此外,COX回归分析表明,m6A风险模型评分是OS的预后因素,FTO上调可能是胃癌患者无复发生存期(RFS)的潜在独立预后因素。:m6A相关基因在GC中失调,与GC患者的预后密切相关。FTO可能是胃癌的一种新型预后生物标志物,而m6A相关风险评分可能有助于风险评估和预后分层。