Clinical Impact of Cellular Senescence and RNA Dysregulation in HCC Is Associated With MASLD and HCV-SVR

The incidence of hepatocellular carcinoma (HCC) associated with metabolic dysfunction-associated steatotic liver disease (MASLD) and hepatitis C virus sustained virologic response (HCV-SVR) are increasing. However, the mechanisms driving HCC development in these patients remain unclear. This study aimed to evaluate the role of cellular senescence and RNA editing in HCC by examining cyclin-dependent kinase inhibitor 2A (p16) and adenosine deaminase acting on RNA (ADAR1) expression.

HCC specimens from patients with MASLD or HCV-SVR were analyzed by immunohistochemistry to assess p16 and ADAR1 expression. Statistical analyses were conducted using the Chi-squared test, Fisher's exact test, and Mann-Whitney U-test. Survival analyses were performed using the Kaplan-Meier method, the log-rank test, and Cox regression analysis.

Among 122 patients, 59 (48.4%) had MASLD and 63 (51.6%) had HCV-SVR. p16 expression was observed in 69 cases (57.0%) in the noncancerous areas and 53 cases (44.5%) in the cancerous areas. ADAR1 expression was positive in 28 cases (23.5%) in the cancerous areas and significantly associated with p16 expression in the cancerous areas (p=0.039). Patients with p16 expression in the noncancerous areas were older (p=0.045) and had elevated serum ALT levels (p=0.024). p16 expression in the cancerous areas were correlated with a shorter recurrence-free survival (HR=1.65, 95%CI=1.00-2.73, p=0.046).

Cellular senescence and RNA editing may play a key role in MASLD- and HCV-SVR-related HCC. p16 expression in the cancerous areas may serve as a prognostic biomarker for surgical outcomes.