Ovarian clear cell
carcinoma (OCCC) has been treated with surgery and
chemotherapy; however, the prognosis remains poor because of chemoresistance. Therefore,
immunotherapies are attracting attention, including the GPC3
peptide vaccine, which improves overall survival. However, the response rate is limited and there are no sufficient predictive
biomarkers that can identify responders before treatment. Our purpose was to identify circulating serum
miRNAs as predictive
biomarkers for response to GPC3
peptide vaccine. Eighty-four patients in a phase II trial of a GPC3
peptide vaccine were enrolled and
miRNA sequencing was performed on their serum samples. Candidate
miRNAs were selected from a group of 14 patients for whom treatment was responsive and validated in an independent group of 10 patients for whom treatment was responsive. Three markedly upregulated
miRNAs, miR-375-3p, miR-193a-5p, and miR-1228-5p, were identified, and the combination of those
miRNAs demonstrated high value in the prediction of the response. The origin of these
miRNAs was assessed by referring to OCCC tissue
miRNA profiles, and they were not identified as
cancer tissue-related
miRNAs. Functional annotation analysis suggested that they were associated with
interferon-related pathways. The
miRNAs identified herein have great potential to allow the realization of liquid biopsy for predicting the
immunotherapy response and
precision medicine.