Systematic expression analysis of m⁶A RNA methyltransferases in clear cell renal cell carcinoma

To investigate the regulation of the N-6-methyladenosine (m⁶A) methyltransferases METTL3, METTL14, WTAP, KIAA1429, and METTL4, referred to as "m⁶A writers," in clear cell renal cell carcinoma (ccRCC), and other RCC subtypes in respect of the potential prognostic value.

Tissue samples were collected within the framework of the Biobank at the Center for Integrated Oncology Bonn. The expression of the methyltransferases was systematically determined in clear cell renal carcinoma (ccRCC) on the RNA (real-time PCR) and protein level (immunohistochemistry). Additionally, protein expression of the m⁶A writers was further investigated in papillary RCC, chromophobe RCC, sarcomatoid RCC, oncocytoma, and normal renal tissue (immunohistochemistry).

The expression of all m⁶A-methyltransferases was significantly downregulated in ccRCC compared to benign renal tissue. Low m⁶A-methyltransferase levels were correlated with higher histological grade, advanced pT-stage, pN-stage, and metastatic disease. Reduced m⁶A-methyltransferase expression was associated with shorter overall survival.

In conclusion, m⁶A-methyltransferases are dysregulated in ccRCC and might act as tumor suppressor genes, which could be of particular importance for future diagnostic and therapeutic options.