TY - JOUR
T1 - Extracellular miRNAs as predictive biomarkers for glypican-3-derived peptide vaccine therapy response in ovarian clear cell carcinoma
AU - Ukai, Mayu
AU - Yokoi, Akira
AU - Yoshida, Kosuke
AU - Suzuki, Shiro
AU - Shibata, Kiyosumi
AU - Kikkawa, Fumitaka
AU - Nakatsura, Tetsuya
AU - Kajiyama, Hiroaki
N1 - Funding Information:
Funding: This study was supported by the Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research (16H05472, 24791698, and 24592512) and the Aichi Cancer Research Foundation.
Funding Information:
Acknowledgments: We express our highest appreciation to all members of the Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, and our works were also supported by the Division for Medical Research Engineering, Nagoya University Graduate School of Medicine. This study was supported by the following: Practical Research for Innovative Cancer Control, grant number 20ck0106630h0001 from the Japan Agency for Medical Research and Development (AMED); the Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research: Grant Number 119H03797 and 20K22806; the Program for Promoting the Enhancement of Research Universities as young researcher units for the advancement of new and undeveloped fields at Nagoya University; the Aichi Cancer Research Foundation; the Yokoyama Foundation for Clinical Pharmacology grant number TRY-2014. The Program for Promoting the Enhancement of Research Universities as young researcher units for the advancement of new and undeveloped fields at Nagoya University also supports this work. Furthermore, we thank Enago (https://www.enago.jp/) for the English editing of this article.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/2/1
Y1 - 2021/2/1
N2 - 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.
AB - 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.
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U2 - 10.3390/cancers13030550
DO - 10.3390/cancers13030550
M3 - Article
AN - SCOPUS:85100071819
VL - 13
SP - 1
EP - 18
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 3
M1 - 550
ER -