Prognostic Implication of the m6A RNA Methylation Regulators in Rectal Cancer

Yajie Chen; Shanshan Wang; William C Cho; Xiang Zhou; Zhen Zhang

doi:10.3389/fgene.2021.604229

Prognostic Implication of the m⁶A RNA Methylation Regulators in Rectal Cancer

Front Genet. 2021 Jun 3:12:604229. doi: 10.3389/fgene.2021.604229. eCollection 2021.

Authors

Yajie Chen^{1

2}, Shanshan Wang^{2

3}, William C Cho⁴, Xiang Zhou^{2

3

5}, Zhen Zhang^{1

2}

Affiliations

¹ Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
² Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
³ Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
⁴ Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, China.
⁵ Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.

Abstract

N6-methyladenosine (m⁶A) is a very common and abundant RNA modifications occurring in nearly all types of RNAs. Although the dysregulated expression of m⁶A regulators is implicated in cancer progression, our understanding of the prognostic value of the m⁶A regulators in rectal cancer is still quite limited. In this study, we analyzed the RNA expression levels of the 17 m⁶A regulator genes of 95 rectal cancer and 10 normal rectal samples from the The Cancer Genome Atlas Rectum Adenocarcinoma (TCGA-READ) dataset. Lasso regression analysis was conducted to build a prognostic model and calculate the risk score. The rectal cancer patients were then devided into the high-risk and low-risk groups according to the mean risk score. The prognostic value of the identified model was separately evaluated in the TCGA-READ and GSE87211 datasets. GSEA was conducted to analyze the functional difference of high-risk and low-risk rectal cancer patients. Our analysis revealed that rectal cancer patients with lower expression of YTHDC2 and METTL14 had a remarkable worse overall survival (P < 0.05). The prognostic value of the model was validated in GSE87211 datasets, with AUC = 0.612 for OS and AUC = 0.651 for RFS. Furthermore, the m⁶A modification-based risk score system is associated with activation of distinct signaling pathways, such as DNA repair, epithelial-mesenchymal transition, G₂M checkpoint and the MYC pathway, that may contribute to the progression of rectal cancer. In conclusion, our findings demonstrated that the m⁶A RNA methylation regulators, specifically YTHDC2 and METTL14, were significantly down-regulated and might be potential prognostic biomarkers in rectal cancer.

Keywords: METTL14; N6-methyladenosine; YTHDC2; prognosis; rectal cancer.