Abstract
m6A, the main form of mRNA modification, participates in regulating multiple normal and pathological biological events, especially in tumorigenesis. However, there is little known about the association of m6A-related genes with prognosis of clear cell renal cell cancer (ccRCC). Therefore, the prognostic value of m6A-related genes was investigated using Kaplan–Meier curves of overall survival (OS) with the log-rank test and Cox regression analysis. The differential expression of YTHDF2 mRNA in ccRCC and tumor-adjacent normal tissues and associated with clinicopathological characteristics was also analyzed. The alteration of cancer signaling pathways was screened by Gene Set Enrichment Analysis (GSEA). Univariate analysis showed that 15 m6A-related genes (including YTHDF2) were closely related to prognosis. Multivariate analysis further confirmed that YTHDF2 could serve as an independent prognostic factor for the OS of ccRCC patients (P < 0.001). Low-level expression of YTHDF2 had poor prognosis in ccRCC patients with lower tumor–node–metastasis (TNM) stage, age > 61, non-distant metastasis, non-lymph node metastasis, female gender, and higher histological grade (P < 0.05). Moreover, YTHDF2 expression in ccRCC tissues (N = 529) is significantly lower than that of tumor-adjacent normal tissues (N = 72, P = 0.0086). Furthermore, GSEA demonstrated that AKT/mTOR/GSK3 pathway, EIF4 pathway, CHREBP2 pathway, MET pathway, NFAT pathway, FAS pathway, EDG1 pathway, and CTCF pathway are altered in tumors with high YTHDF2 expression. Taken together, our results demonstrated that YTHDF2 (an m6A-related gene) could serve as a potential prognostic biomarker of ccRCC, and targeting epigenetic modification may be a novel therapeutic strategy for the treatment of ccRCC.
Highlights
In 2018, 65,340 new cases of renal cell carcinoma (RCC) were diagnosed and 14,970 resulted deaths in the United States [1]
We discovered that several specific m6A-related genes were closely related to distinct overall survival (OS) and that YTHDF2 can serve as an independent risk factor in clear cell renal cell cancer (ccRCC)
Our result showed that YTHDF2 mRNA expression significantly correlated with histological grade and sex
Summary
In 2018, 65,340 new cases of renal cell carcinoma (RCC) were diagnosed and 14,970 resulted deaths in the United States [1]. ∼3/4 of RCC belongs to clear cell renal cell cancer (ccRCC) [2]. There are three main treatment measures for ccRCC, including radiotherapy, chemotherapy, and surgical resection [3,4,5]. The primary therapeutic measure for metastatic RCC (mRCC) is antiangiogenic therapy-based targeting tyrosine kinase. This treatment is of benefit for mRCC patients, and the reason for limited efficacy is development of drug resistance [7, 8], this biochemical alteration leads to poorer prognosis [9]. Understanding the precise mechanisms of mRCC and looking for the key clinical biomarker and therapeutic target for RCC metastasis will contribute to successful treatment ccRCC
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