PMID- 28789351 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 1792-1074 (Print) IS - 1792-1082 (Electronic) IS - 1792-1074 (Linking) VI - 14 IP - 2 DP - 2017 Aug TI - miR-196b, miR-378a and miR-486 are predictive biomarkers for the efficacy of vaccine treatment in colorectal cancer. PG - 1355-1362 LID - 10.3892/ol.2017.6303 [doi] AB - MicroRNAs (miRNAs/miRs) regulate the levels of transcripts and serve a critical function in the regulation of tumor microenvironments. Therefore, miRNA levels in cancer tissues are thought to be potential biomarkers for immunotherapy. From a phase I trial of a vaccine treatment using 5 human leukocyte antigen (HLA)-A*2402-restricted peptides (registration no. UMIN000004948), colorectal cancer (CRC) tissues were obtained from 8 patients and normal colorectal tissues from 5 patients via surgery. From a phase II trial using the same peptides (registration no. UMIN000001791), CRC tissues were obtained from 16 patients from the HLA-A*2402-matched group and 10 patients from the HLA-A*2402-unmatched group. These tissues were used for miRNA microarray analysis. As the first step, cancer tissues from the phase I study were used and 10 candidate miRNAs were selected by comparing the miRNA expression between two groups; one with improved prognosis and the other with poor prognosis. The miRNAs were subsequently validated using the cases enrolled in the phase II study. Significantly improved prognoses were identified in 16 patients in the HLA-A*2402-matched group with high expression of miR-196b-5p and low expression of miR-378a-3p and miR-486-5p. There was no difference in prognosis in the 10 patients in the HLA-A*2402-unmatched group. Therefore, high miR-196b expression and low miR-378a-3p and miR-486-5p expression were indicated as useful biomarkers for prediction of the efficacy of vaccine treatment for patients with metastatic CRC. In a planned phase III study, expression levels of these 3 miRNAs (miR-196b-5p, miR-378a-3p and miR-486-5p) may be useful biomarkers for assessing patients who are likely to have an improved outcome following vaccination. FAU - Shindo, Yoshitaro AU - Shindo Y AD - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan. FAU - Hazama, Shoichi AU - Hazama S AD - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan. FAU - Nakamura, Yusuke AU - Nakamura Y AD - Department of Medicine and Surgery, The University of Chicago, Chicago, IL 60637, USA. FAU - Inoue, Yuka AU - Inoue Y AD - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan. FAU - Kanekiyo, Shinsuke AU - Kanekiyo S AD - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan. FAU - Suzuki, Nobuaki AU - Suzuki N AD - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan. FAU - Takenouchi, Hiroko AU - Takenouchi H AD - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan. FAU - Tsunedomi, Ryouichi AU - Tsunedomi R AD - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan. FAU - Nakajima, Masao AU - Nakajima M AD - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan. FAU - Ueno, Tomio AU - Ueno T AD - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan. FAU - Takeda, Shigeru AU - Takeda S AD - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan. FAU - Yoshino, Shigefumi AU - Yoshino S AD - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan. FAU - Okuno, Kiyotaka AU - Okuno K AD - Department of Surgery, Kinki University Faculty of Medicine, Osakasayama, Osaka 589-8511, Japan. FAU - Fujita, Yusuke AU - Fujita Y AD - Department of Computer Science and Systems Engineering, Faculty of Engineering, Yamaguchi University, Ube, Yamaguchi 755-8611, Japan. FAU - Hamamoto, Yoshihiko AU - Hamamoto Y AD - Department of Computer Science and Systems Engineering, Faculty of Engineering, Yamaguchi University, Ube, Yamaguchi 755-8611, Japan. FAU - Kawakami, Yutaka AU - Kawakami Y AD - Division of Cellular Signaling, Institute for Advanced Medical Research; Keio University School of Medicine, Tokyo 160-8582, Japan. FAU - Oka, Masaaki AU - Oka M AD - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan. FAU - Nagano, Hiroaki AU - Nagano H AD - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan. LA - eng PT - Journal Article DEP - 20170602 PL - Greece TA - Oncol Lett JT - Oncology letters JID - 101531236 PMC - PMC5529876 OTO - NOTNLM OT - colorectal cancer OT - efficacy OT - microRNA OT - peptide vaccine OT - predictive biomarker EDAT- 2017/08/10 06:00 MHDA- 2017/08/10 06:01 PMCR- 2017/06/02 CRDT- 2017/08/10 06:00 PHST- 2016/02/17 00:00 [received] PHST- 2017/03/09 00:00 [accepted] PHST- 2017/08/10 06:00 [entrez] PHST- 2017/08/10 06:00 [pubmed] PHST- 2017/08/10 06:01 [medline] PHST- 2017/06/02 00:00 [pmc-release] AID - OL-0-0-6303 [pii] AID - 10.3892/ol.2017.6303 [doi] PST - ppublish SO - Oncol Lett. 2017 Aug;14(2):1355-1362. doi: 10.3892/ol.2017.6303. Epub 2017 Jun 2.