EXOSOMAL MIRNA AS A VALUABLE INDICATOR FOR PREDICTING THE RESPONSE OF ATEZOLIZUMAB AND BEVACIZUMAB COMBINATION THERAPY IN PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA

초록

Background: Atezolizumab and bevacizumab combination therapy is the frontline treatment for advanced hepatocellular carcinoma, but identifying a reliable biomarker for predicting treatment response remains elusive. This study aimed to identify exosomal miRNA biomarkers that could forecast favorable responses to this combination therapy. Methods: Blood samples were collected from patients with advanced hepatocellular carcinoma before initiating the atezolizumab and bevacizumab treatment Patients were categorized into responders (those exhibiting stable disease, partial, or complete response) and non-responders (those showing disease progression). Serum was concentrated using a qEV concentration and isolation kit, followed by extraction of exosomal RNA for small RNA sequencing via next-generation sequencing (NGS). Decision tree analysis was employed to identify miRNAs from the top 100 most expressed that effectively differentiated between responders and nonresponders. The results were validated using a t-test. Results: The study comprised eight patients in each group, predominantly male, with seven out of eight patients in both groups having viral-induced hepatocellular carcinoma. NGS yielded 1076 miRNAs, among which 12 exhibited significant differential expression between responders and non-responders. Three miRNAs were notably elevated, while nine were decreased in the responder group. Notably, let7c-5p, miR-30a-5p, and miR192-5p were significantly increased in responders. Decision tree analysis identified 30 miRNAs from the top 100, with miR-30a-5p showing significantly higher levels in responders (p = 0.0047). Quantitative reverse transcription PCR validation confirmed the increased expression of miR-30a-5p in responders compared to non-responders. Additionally, transfection of miR-30a-5p into HepG2 cells resulted in decreased migration and proliferation . Conclusion: Exosomal miRNAs hold promise as biomarkers for predicting response to atezolizumab-bevacizumab therapy.