Low Tumor miR-369-3p Levels Combined with Plasma Hepatitis B Virus Pre-S2 Gene Deletion Mutation Predict Higher Hepatocellular Carcinoma Recurrence

Introduction: Although resection surgery is a curative treatment for hepatocellular carcinoma (HCC), high HCC recurrence leads to poor patient survival. Chronic hepatitis B virus (HBV) infection is an important risk factor for HCC. Deletion mutation in HBV pre-S2 gene results in expression of pre-S2 mutant oncoprotein and represents an independent prognostic biomarker for HCC recurrence. MicroRNAs (miRNAs) are small non-coding RNAs that play key roles in HBV-related HCC. Methods: This study aimed to identify the miRNAs whose expression levels in tumor tissues were correlated with pre-S2 gene deletion mutation and post-resection HCC recurrence and investigate their potential in combination with pre-S2 gene deletion mutation to predict HCC recurrence in a retrospective cohort of patients. Results: The results showed that the expression level of miR-369-3p was decreased in tumor tissues of patients with pre-S2 gene deletion mutation or HCC recurrence. miR-369-3p was identified as a prognostic biomarker for HCC recurrence. Patients with pre-S2 gene deletion mutation combined with a low level of miR-369-3p had a higher risk of HCC recurrence than patients with either one or none of these two biomarkers. The combination of pre-S2 gene deletion mutation and miR-369-3p expression level showed a greater prognostic potential for HCC recurrence than either biomarker alone. Conclusion: Collectively, miR-369-3p held exploratory promise in serving as a combination biomarker with pre-S2 gene deletion mutation to provide a better potential in predicting HBV-related HCC recurrence after curative surgical resection. Plain Language Summary: This study provided preliminary evidence indicating a negative association between HBV pre-S2 gene deletion mutation and miR-369-3p expression level in tumor tissues of HCC patients and demonstrating a superior prognostic potential of combining these two biomarkers for post-resection HCC recurrence.