Exosomal miR-30a-5p: a promising biomarker for predicting response to Atezolizumab-Bevacizumab therapy in advanced hepatocellular carcinoma

초록

Background and aims: Atezolizumab and bevacizumab combination therapy is currently the first-line treatment for advanced hepatocellular carcinoma. However, iVdentifying a reliable biomarker to predict treatment response remains challenging. This study aimed to discover exosomal miRNA biomarkers that could forecast positive responses to this combination therapy. Method: Blood samples were collected from patients with advanced hepatocellular carcinoma before they began treatment with atezolizumab and bevacizumab. Patients were categorized into two groups: responders, who exhibited stable disease or showed partial or complete response to the treatment, and non-responders, who demonstrated disease progression. To isolate the exosomes, the serum samples were concentrated using a qEV concentration and isolation kit. Following this, exosomal RNA were extracted from the concentrated samples. The extracted RNAwas then subjected to small RNA sequencing using next-generation sequencing (NGS) technology to identify the miRNAs present in the samples. Decision tree analysis was employed to identify miRNAs from the top 100 most expressed that effectively differentiated between responders and nonresponders. Results: The research included a total of 16 patients, evenly divided between responders and non-responders, with a predominance of male subjects and a high prevalence of viral-induced hepatocellular carcinoma in both groups. Next-generation sequencing analysis identified a total of 1076 miRNAs, among which 12 exhibited significant differential expression between the responder and nonresponder groups. Notably, three miRNAs - let7c-5p, miR-30a-5p, and miR192-5p - were found to be significantly elevated in the responder group. Further analysis using decision tree methodology identified 30 miRNAs from the top 100 most expressed, with miR-30a-5p emerging as a particularly promising candidate, showing significantly higher levels in responders (p = 0.0047). The increased expression of miR-30a-5p in responders was subsequently confirmed through quantitative reverse transcription PCR validation. Additionally, in vitro experiments demonstrated that transfection of miR-30a-5p into HepG2 cells resulted in decreased cell migration and proliferation, suggesting a potential mechanistic link between this miRNA and treatment response. Conclusion: Exosomal miRNAs show promise as potential biomarkers for predicting response to atezolizumab-bevacizumab therapy in advanced hepatocellular carcinoma. This research provides a foundation for further investigation into using these biomarkers to optimize treatment strategies for patients with this aggressive form of liver cancer.