Novel Prognostic Implications of Methylated RNA and Demethylases in Resected HCC and Background Liver Tissue

Abstract

Background/Aim: N6-Methyladenosine (m6A), the most abundant internal modification of RNA, plays a critical role in cancer development. However, the clinical implications of m⁶A in hepatocellular carcinoma (HCC) remain unclear. Materials and Methods: We analyzed 177 HCC and paired noncancerous liver tissues from patients who underwent hepatectomy according to global m⁶A quantification and expression of m⁶A demethylases fat mass and obesity-associated protein (FTO) and alpha-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5). Results: The global m⁶A quantification revealed no significant difference between HCC and non-cancerous tissue. The expression of m⁶A demethylases FTO and ALKBH5, was significantly lower in HCC than in non-cancerous tissues (both p<0.001). Furthermore, low ALKBH5 expression in non-cancerous tissues was significantly correlated with worse recurrence-free survival (median of 16.3 vs. 38.9 months, p=0.001). Conclusion: m⁶A in HCC and its demethylase in surrounding non-cancerous liver tissues might be involved in inherent mechanisms for HCC development and affect malignant potential after HCC resection.