Novel prognostic implications of YTH domain family 2 in resected hepatocellular carcinoma

N6-methyladenosine (m(6)A), the most abundant internal RNA modification, serves a critical role in cancer development. However, the clinical implications of m(6)A in hepatocellular carcinoma (HCC) remain unclear. The present study sought to reveal the potential roles of m(6)A readers, which recognize m(6)A, in HCC. A total of 177 HCC and paired non-cancerous liver tissues from patients who underwent hepatectomy were analysed using quantitative PCR for the expression of m(6)A readers: YT521-B homology domain family 1 (YTHDF1) and YT521-B homology domain family 2 (YTHDF2). The expression levels of both YTHDF1 and YTHDF2 were not significantly different between tumour and non-cancerous tissues (P=0.93 and P=0.7, respectively). Analysis of the association between clinical features and m(6)A reader expression revealed that YTHDF1 expression was associated with formation of capsule (P=0.02), whereas low YTHDF2 expression was associated with septal formation (P=0.02). Furthermore, high YTHDF1 expression and high YTHDF2 expression were significantly associated with shorter recurrence-free survival (RFS) [YTHDF1: Mean survival time (MST), 34.0 vs. 19.0 months, P=0.014; YTHDF2: MST, 30.1 vs. 12.9 months, P=0.0032], whereas YTHDF1 and YTHDF2 expression was not significantly associated with overall survival (OS) (YTHDF1: MST, 99.4 vs. 70.2 months, P=0.74; YTHDF2: MST, 98.4 vs. 64.1 months, P=0.28). According to multivariate analysis, serosal invasion [hazard ratio (HR), 2.39; 95% CI 1.30–4.42; P=0.005), portal vein or hepatic vein invasion (HR, 2.82; 95% CI 1.26–6.28; P=0.01) and YTHDF2 expression in HCC tissues (HR, 1.85; 95% CI 1.09–3.15; P=0.02) were identified as significant independent prognostic factors for RFS. α-fetoprotein (HR, 1.79; 95% CI 1.10–2.92; P=0.02), serosal invasion (HR, 1.99; 95% CI 1.17–3.34; P=0.01) and portal vein or hepatic vein invasion (HR, 3.02; 95% CI 1.38–6.61; P=0.006) were identified as significant independent prognostic factors for OS. In conclusion, the present study revealed that high YTHDF2 expression, an m(6)A reader, in HCC tissues was associated with cancer recurrence.