基于癌症基因组图谱（TCGA）中m6A甲基化相关基因评估食管鳞状细胞癌的预后。
Estimating the prognosis of esophageal squamous cell carcinoma based on The Cancer Genome Atlas (TCGA) of m6A methylation-associated genes.
作者信息
Pu Yu, Lu Xianfeng, Yang Xueqin, Yang Yi, Wang Dong, Li Mengxia, Guan Wei, Xu Mingfang
机构信息
Cancer Center of Daping Hospital, Army Medical University, Chongqing, China.
出版信息
J Gastrointest Oncol. 2022 Feb;13(1):1-12. doi: 10.21037/jgo-21-686.
BACKGROUND
N6-methyladenosine (m6A) mRNA modification is the most prevalent in certain tumors. However, its expression profile and prognostic value in human esophageal squamous cell carcinoma (ESCC) remains unknown.
METHODS
Herein, we performed an extensive investigation of the m6A-associated gene expression profile and determined its significance in the prognosis of ESCC. We received the RNA expression profiles of 81 ESCC tissues and one normal esophageal tissue from The Cancer Genome Atlas (TCGA) database. Kaplan-Meier (KM) survival analysis was used to assess the predictability of m6A methylation-associated gene expression in ESCC prognosis. In addition, univariate and multivariate Cox regression, as well as least absolute shrinkage and selection operator (LASSO) regression models were employed for the establishment of prognostic signatures. Lastly, KM survival analysis, proportional hazard models, and receiver operating characteristic (ROC) curves were used to verify the prognostic value. Moreover, we also investigated the associations among the m6A prognostic signature, immune cell infiltration, and programmed cell death-ligand 1 () expression.
RESULTS
We demonstrated that [hazard ratio (HR): 0.910; 95% confidence interval (CI): 0.832-0.995; P=0.038], (HR: 0.721; 95% CI: 0.549-0.948; P=0.019), (HR: 0.801; 95% CI: 0.664-0.967; P=0.021), and (HR: 0.948; 95% CI: 0.895-1.003; P=0.0.064) overexpression predicted better overall survival (OS) of ESCC patients. Furthermore, based on prognostic factors, the high-risk (H-R) cohort was found to have worse survival than the low-risk (L-R) cohort (P<0.001).
CONCLUSIONS
We revealed three m6A methylation-associated genes that were closely correlated with enhanced survival in ESCC patients. In addition, we generated an independent prognostic signature based on the expression of , , , and genes. The results revealed significantly higher proportions of CD8 T cells and higher expression of in the H-R group.
背景
N6-甲基腺苷（m6A）mRNA修饰在某些肿瘤中最为普遍。然而，其在人类食管鳞状细胞癌（ESCC）中的表达谱及预后价值仍不清楚。
方法
在此，我们对m6A相关基因表达谱进行了广泛研究，并确定了其在ESCC预后中的意义。我们从癌症基因组图谱（TCGA）数据库中获取了81例ESCC组织和1例正常食管组织的RNA表达谱。采用Kaplan-Meier（KM）生存分析评估m6A甲基化相关基因表达对ESCC预后的预测能力。此外，运用单因素和多因素Cox回归以及最小绝对收缩和选择算子（LASSO）回归模型建立预后特征。最后，采用KM生存分析、比例风险模型和受试者工作特征（ROC）曲线验证预后价值。此外，我们还研究了m6A预后特征、免疫细胞浸润和程序性细胞死亡配体1（）表达之间的关联。
结果
我们证明[风险比（HR）：0.910；95%置信区间（CI）：0.832 - 0.995；P = 0.038]、（HR：0.721；95% CI：0.549 - 0.948；P = 0.019）、（HR：0.801；95% CI：0.664 - 0.967；P = 0.021）和（HR：0.948；95% CI：0.895 - 1.003；P = 0.0.064）的过表达预示ESCC患者有更好的总生存期（OS）。此外，基于预后因素，发现高风险（H - R）队列的生存期比低风险（L - R）队列更差（P < 0.001）。
结论
我们揭示了三个与ESCC患者生存期延长密切相关的m6A甲基化相关基因。此外，我们基于、、和基因的表达生成了一个独立的预后特征。结果显示，高风险组中CD8 T细胞比例显著更高，表达也更高。
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