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

Nobuhiko Nakagawa; Fuminori Sonohara; Katsuhito Tanaka; Yuki Sunagawa; Yoshikuni Inokawa; Hideki Takami; Masamichi Hayashi; Suguru Yamada; Mitsuro Kanda; Chie Tanaka; Goro Nakayama; Masahiko Koike; Yasuhiro Kodera

doi:10.3892/ol.2021.12799

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

Oncol Lett. 2021 Jul;22(1):538. doi: 10.3892/ol.2021.12799. Epub 2021 May 19.

Affiliation

¹ Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.

Abstract

N6-methyladenosine (m⁶A), the most abundant internal RNA modification, serves a critical role in cancer development. However, the clinical implications of m⁶A in hepatocellular carcinoma (HCC) remain unclear. The present study sought to reveal the potential roles of m⁶A readers, which recognize m⁶A, 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 m⁶A 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 m⁶A 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 m⁶A reader, in HCC tissues was associated with cancer recurrence.

Keywords: YTH domain family; hepatocellular carcinoma; methylation of N6 adenosine; prognosis.

Grants and funding

The present study was partly supported by the Japan Society for the Promotion of Science KAKENHI Grant-in-Aid for Scientific Research (grant nos. 18H06176 and 19K18110).