Molecular subtypes of m⁶A RNA methylation modification patterns and their clinical significance in clear cell renal...

In this study, we sought to investigate the association between N6-methyladenosine (m⁶A) RNA methylation-modification patterns and patient prognosis in clear cell renal cell carcinoma (ccRCC) and construct a ccRCC molecular signature according to expressions of m⁶A-related genes.

First, the clinical data and the transcriptomes of 530 patients with ccRCC were downloaded from The Cancer Genome Atlas (TCGA). The expression patterns of m⁶A-related genes were extracted, and the differences in m⁶A-modification patterns between normal and tumor renal tissues were analyzed. To explore the prognostic role of m⁶A-modification patterns a in ccRCC, the molecular subtypes of ccRCC were identified based on the expression patterns of the m⁶A-related genes, and survival rates in patients with the different subtypes were compared. According to expressions of m⁶A-related genes and clinical prognosis data, a prognostic molecular signature was constructed using least absolute shrinkage and selector operation (LASSO)-Cox regression analysis.

Among the 13 m⁶A -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 m⁶A-related genes were associated with differential clinical outcomes.

Following TCGA data-mining, different molecular subtypes of ccRCC based on m⁶A RNA methylation patterns were found to have different prognoses. The molecular signature constructed according to the expression patterns of m⁶A-related genes could predict patient prognosis in ccRCC. We believe m⁶A RNA methylation modification is a potential therapeutic target and may play a crucial role in ccRCC.