Estimating the prognosis of esophageal squamous cell carcinoma based on The Cancer Genome Atlas (TCGA) of m6A methylation-associated genes

Yu Pu; Xianfeng Lu; Xueqin Yang; Yi Yang; Dong Wang; Mengxia Li; Wei Guan; Mingfang Xu

doi:10.21037/jgo-21-686

Estimating the prognosis of esophageal squamous cell carcinoma based on The Cancer Genome Atlas (TCGA) of m6A methylation-associated genes

J Gastrointest Oncol. 2022 Feb;13(1):1-12. doi: 10.21037/jgo-21-686.

Authors

Yu Pu^#¹, Xianfeng Lu^#¹, Xueqin Yang¹, Yi Yang¹, Dong Wang¹, Mengxia Li¹, Wei Guan¹, Mingfang Xu¹

Affiliation

¹ Cancer Center of Daping Hospital, Army Medical University, Chongqing, China.

^# Contributed equally.

Abstract

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 (PD-L1) expression.

Results: We demonstrated that YTHDF3 [hazard ratio (HR): 0.910; 95% confidence interval (CI): 0.832-0.995; P=0.038], RBM15 (HR: 0.721; 95% CI: 0.549-0.948; P=0.019), KIAA1429 (HR: 0.801; 95% CI: 0.664-0.967; P=0.021), and ALKBH5 (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 YTHDF3, RBM15, KIAA1429, and ALKBH5 genes. The results revealed significantly higher proportions of CD8⁺ T cells and higher expression of PD-L1 in the H-R group.

Keywords: N6-methyladenosine (m6A); RNA methylation; esophageal squamous cell carcinoma (ESCC); immune cell infiltration; prognosis.