Exosomal miRNA as a biomarker for predicting response of atezolizumab and bevacizumab in hepatocellular carcinoma

초록

Objectives: Atezolizumab and bevacizumab combination therapy is currently used for patients with advanced hepatocellular carcinoma, but biomarkers for response to systemic therapy is unknown. This study aimed to find exosomal miRNA biomarkers to predict response to combination therapy. Materials and Methods: Sera were collected from patients with advanced hepatocellular carcinoma before the first cycle treatment of atezolizumab and bevacizumab. The patients were divided into two groups; the response group comprised patients showing stable disease, partial or complete response, while the non-response group consisted of patients showing progressive disease. The serum was concentrated with qEV concentration and isolation kit. Exosomal RNA was extracted from isolates and small RNA sequencing using next-generation sequencing (NGS) was performed. We selected miRNAs that effectively distinguished between response or non-response using decision tree analysis among the top 100 in the order of most expressed. T-test was used to verify decision tree results. Results: Eight patients each were included in the response and non-response group. A total of 1,076 miRNA were obtained from NGS. Among 1,076 miRNAs, 12 miRNAs showed significant difference in expression between response group and non-response group. Three miRNAs significantly increased and 9 miRNAs significantly decreased in response group. Significantly increased miRNAs in response group were let7c-5p, miR-30a-5p, and miR192-5p. Out of top 100 most read miRNAs, 30 miRNAs were selected by decision tree analysis. miR-30a-5p levels were significantly higher in good response group (P = 0.0047). Conclusion: Exosomal miRNAs could be used as a biomarker for predicting response to atezolizumab-bevacizumab therapy.