Xu Xin, Zhou En, Zheng Jun, Zhang Chihao, Zou Yinghua, Lin Jiayun, Yu Jiwei
Department of General Surgery, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of Cardiology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Front Oncol. 2021 Feb 26;11:631803. doi: 10.3389/fonc.2021.631803. eCollection 2021.
N6-methyladenosine (m6A) RNA modification plays a critical role in gastric cancer (GC). However, the relationship between the m6A "eraser", FTO, and ALKBH5, and the prognosis of GC still remains unclear. This study aimed to evaluate the effect of FTO and ALKBH5 on the prognosis of patients and their potential roles in GC.
A total of 738 GC samples with clinical information obtained from two independent datasets were included and divided into training set and testing set. Differential expression analysis of the m6A "eraser" related genes was performed. The LASSO Cox regression model was constructed to analyze the m6A "eraser" related risk genes. The univariate and multivariate Cox regression model were employed to identify the independent prognostic factors. Kaplan-Meier method was used for survival analysis. A nomogram model was then carried out to predict the prognosis of GC patients. Additionally, GO and KEGG analyses were conducted to identify the potential role of the m6A "eraser" related genes in GC. The relative proportion of 22 different genotypes in immune infiltrating cells was calculated by CIBERSORT algorithm.
In total, nine m6A "eraser" related risk genes and risk scores were obtained and calculated. Patients in high-risk group demonstrated significantly worse prognosis than those in low-risk group. Age, stage, and risk score were considered as independent prognostic factors. The nomogram model constructed accurately predicted the 3-year and 5-year overall survival (OS) of patients. Furthermore, m6A "eraser" might play a functional role in GC. The expression of m6A "eraser" leads to changes in tumor immune microenvironment.
FTO and ALKBH5 showed association with the prognosis of GC. The m6A "eraser" related genes, which is considered as a reliable prognostic and predictive tool, assists in predicting the OS in GC patients.
N6-甲基腺苷（m6A）RNA修饰在胃癌（GC）中起关键作用。然而，m6A“去甲基化酶”FTO和ALKBH5与GC预后之间的关系仍不清楚。本研究旨在评估FTO和ALKBH5对患者预后的影响及其在GC中的潜在作用。
纳入从两个独立数据集中获取的738份具有临床信息的GC样本，并分为训练集和测试集。对m6A“去甲基化酶”相关基因进行差异表达分析。构建LASSO Cox回归模型以分析m6A“去甲基化酶”相关风险基因。采用单因素和多因素Cox回归模型确定独立预后因素。采用Kaplan-Meier法进行生存分析。然后构建列线图模型以预测GC患者的预后。此外，进行基因本体（GO）和京都基因与基因组百科全书（KEGG）分析以确定m6A“去甲基化酶”相关基因在GC中的潜在作用。通过CIBERSORT算法计算免疫浸润细胞中22种不同基因型的相对比例。
共获得并计算了9个m6A“去甲基化酶”相关风险基因和风险评分。高危组患者的预后明显比低危组差。年龄、分期和风险评分被视为独立预后因素。构建的列线图模型准确预测了患者的3年和5年总生存期（OS）。此外，m6A“去甲基化酶”可能在GC中发挥功能作用。m6A“去甲基化酶”的表达导致肿瘤免疫微环境发生变化。
FTO和ALKBH5与GC预后相关。m6A“去甲基化酶”相关基因可作为一种可靠的预后和预测工具，有助于预测GC患者的OS。
