Molecular subtypes of m(6)A RNA methylation modification patterns and their clinical significance in clear cell renal cell carcinoma

BACKGROUND: In this study, we sought to investigate the association between N6-methyladenosine (m(6)A) RNA methylation-modification patterns and patient prognosis in clear cell renal cell carcinoma (ccRCC) and construct a ccRCC molecular signature according to expressions of m(6)A-related genes. METHODS: First, the clinical data and the transcriptomes of 530 patients with ccRCC were downloaded from The Cancer Genome Atlas (TCGA). The expression patterns of m(6)A-related genes were extracted, and the differences in m(6)A-modification patterns between normal and tumor renal tissues were analyzed. To explore the prognostic role of m(6)A-modification patterns a in ccRCC, the molecular subtypes of ccRCC were identified based on the expression patterns of the m(6)A-related genes, and survival rates in patients with the different subtypes were compared. According to expressions of m(6)A-related genes and clinical prognosis data, a prognostic molecular signature was constructed using least absolute shrinkage and selector operation (LASSO)-Cox regression analysis. RESULTS: Among the 13 m(6)A -related genes identified in this study, 8 (YTHDC1, YTHDF2, HNRNPC, METTL14, ZC3H13, FTO, YTHDC2, and YTHDF1) showed significant expression differences between normal and tumor renal tissues. The molecular subtypes of ccRCC identified according to their expression of the 13 m(6)A-related genes were associated with differential clinical outcomes. CONCLUSIONS: Following TCGA data-mining, different molecular subtypes of ccRCC based on m(6)A RNA methylation patterns were found to have different prognoses. The molecular signature constructed according to the expression patterns of m(6)A-related genes could predict patient prognosis in ccRCC. We believe m(6)A RNA methylation modification is a potential therapeutic target and may play a crucial role in ccRCC.