Gene signatures and prognostic values of m6A regulators in clear cell renal cell carcinoma – a retrospective study using TCGA database

Abstract

m6A is the most common form of mRNA modification. However, little is known about its role in clear cell renal cell carcinoma (ccRCC). This study aims to identify gene signatures and prognostic values of m6A regulators in ccRCC. In this study, a total of 528 ccRCC patients from TCGA database with sequencing and CNV data were included. Survival analysis was performed using log-rank tests and Cox regression model. The association between alteration of m6A regulators and clinicopathological characteristics was examined using chi-square test. The results showed that alteration of m6A regulators was associated with pathologic stage. Patients with any CNVs of the regulatory genes had worse OS and DFS than those with diploid genes. Moreover, deletion of m6A “writer” genes was an independent risk factor for OS, and copy number gain of “eraser” genes could magnify the effect in a synergistic way. Additionally, low expression of the writer gene METTL3 was related to activations of adipogenesis and mTOR pathways. Thus, we for the first time determined genetic alterations of m6A regulators in ccRCC and found a significant relationship between the alterations and worse clinical characteristics. The findings provide us clues to understand epigenetic modification of RNA in ccRCC.

Diagnostic, progressive and prognostic performance of m6A methylation RNA regulators in lung adenocarcinoma

“…There were 13 m 6 A RNA methylation genes brought into the study, namely, METTL3, METTL14, WTAP, KIAA1429, RBM15, ZC3H13, YTHDC1, YTHDC2, YTHDF1, YTHDF2, HNRNPC, FTO, and ALKBH5 [45,46]. We investigated their role in diagnosis, progression, and prognosis of lung adenocarcinoma of both training and validation cohort.…”

Multiple Functions and Mechanisms Underlying the Role of METTL3 in Human Cancers

“…METTL3 has been demonstrated to be dysregulated in diverse human malignancies and involved in many aspects of carcinogenesis. Zhou et al showed that METTL3 and METTL14 exhibited higher expression in clear cell renal cell carcinoma than in normal samples and that patients with deletion of METTL3 had poorer overall survival (OS) and disease-free survival (DFS) (22). Liu et al revealed that the proliferation, viability, and migration of gastric cancer cells with METTL3 silencing in vitro were significantly inhibited compared with those of control cells (23).…”

The prognostic values of m6A RNA methylation regulators in Uveal melanoma

“…The different expression of these m6A regulators may eventually lead to the various of survival outcomes. [21] Among the m6A regulators, previous studies indicated that the eraser ALKBH5 can induce breast cancer stem cell and glioblastoma stem-like cell proliferation and tumor initiation, [22] the writers METTL3 and METTL14 were reported to enhance glioblastoma growth and suppress Liver cancer metastasis, [23][24][25] the reader YTHDF1 and YTHDF2 induce cancer cell proliferation in colon cancer and lung oncogenic effects. [26,27] These ndings manifested that high or low expression of speci c m6A regulators are related to misregulation of RNAs in tumors, and the same m6A regulator may take different functions in various tumors.…”