miR-196b, miR-378a and miR-486 are predictive biomarkers for the efficacy of vaccine treatment in colorectal cancer

Shindo,Yoshitaro; Hazama,Shoichi; Nakamura,Yusuke; Inoue,Yuka; Kanekiyo,Shinsuke; Suzuki,Nobuaki; Takenouchi,Hiroko; Tsunedomi,Ryouichi; Nakajima,Masao; Ueno,Tomio; Takeda,Shigeru; Yoshino,Shigefumi; Okuno,Kiyotaka; Fujita,Yusuke; Hamamoto,Yoshihiko; Kawakami,Yutaka; Oka,Masaaki; Nagano,Hiroaki

doi:10.3892/ol.2017.6303

miR-196b, miR-378a and miR-486 are predictive biomarkers for the efficacy of vaccine treatment in colorectal cancer

Authors:
- Yoshitaro Shindo
- Shoichi Hazama
- Yusuke Nakamura
- Yuka Inoue
- Shinsuke Kanekiyo
- Nobuaki Suzuki
- Hiroko Takenouchi
- Ryouichi Tsunedomi
- Masao Nakajima
- Tomio Ueno
- Shigeru Takeda
- Shigefumi Yoshino
- Kiyotaka Okuno
- Yusuke Fujita
- Yoshihiko Hamamoto
- Yutaka Kawakami
- Masaaki Oka
- Hiroaki Nagano
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Affiliations: Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755‑8505, Japan, Department of Medicine and Surgery, The University of Chicago, Chicago, IL 60637, USA, Department of Surgery, Kinki University Faculty of Medicine, Osakasayama, Osaka 589‑8511, Japan, Department of Computer Science and Systems Engineering, Faculty of Engineering, Yamaguchi University, Ube, Yamaguchi 755‑8611, Japan, Division of Cellular Signaling, Institute for Advanced Medical Research; Keio University School of Medicine, Tokyo 160‑8582, Japan
Published online on: June 2, 2017 https://doi.org/10.3892/ol.2017.6303
Pages: 1355-1362
Copyright: © Shindo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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1	Zaharie F, Muresan MS, Petrushev B, Berce C, Gafencu GA, Selicean S, Jurj A, Cojocneanu-Petric R, Lisencu CI, Pop LA, et al: Exosome-carried microRNA-375 inhibits cell progression and dissemination via Bcl-2 blocking in colon cancer. J Gastrointestin Liver Dis. 24:435–443. 2015.PubMed/NCBI
2	Takeyama H, Yamamoto H, Yamashita S, Wu X, Takahashi H, Nishimura J, Haraguchi N, Miyake Y, Suzuki R, Murata K, et al: Decreased miR-340 expression in bone marrow is associated with liver metastasis of colorectal cancer. Mol Cancer Ther. 13:976–985. 2014. View Article : Google Scholar : PubMed/NCBI
3	Konno Y, Dong P, Xiong Y, Suzuki F, Lu J, Cai M, Watari H, Mitamura T, Hosaka M, Hanley SJ, et al: MicroRNA-101 targets EZH2, MCL-1 and FOS to suppress proliferation, invasion and stem cell-like phenotype of aggressive endometrial cancer cells. Oncotarget. 5:6049–6062. 2014. View Article : Google Scholar : PubMed/NCBI
4	Achberger S, Aldrich W, Tubbs R, Crabb JW, Singh AD and Triozzi PL: Circulating immune cell and microRNA in patients with uveal melanoma developing metastatic disease. Mol Immunol. 58:182–186. 2014. View Article : Google Scholar : PubMed/NCBI
5	Okada H, Kohanbash G and Lotze MT: MicroRNAs in immune regulation-opportunities for cancer immunotherapy. Int J Biochem Cell Biol. 42:1256–1261. 2010. View Article : Google Scholar : PubMed/NCBI
6	Hazama S, Nakamura Y, Takenouchi H, Suzuki N, Tsunedomi R, Inoue Y, Tokuhisa Y, Iizuka N, Yoshino S, Takeda K, et al: A phase I study of combination vaccine treatment of five therapeutic epitope-peptides for metastatic colorectal cancer; safety, immunological response, and clinical outcome. J Transl Med. 12:632014. View Article : Google Scholar : PubMed/NCBI
7	Suzuki N, Hazama S, Ueno T, Matsui H, Shindo Y, Iida M, Yoshimura K, Yoshino S, Takeda K and Oka M: A phase I clinical trial of vaccination with KIF20A-derived peptide in combination with gemcitabine for patients with advanced pancreatic cancer. J Immunother. 37:36–42. 2014. View Article : Google Scholar : PubMed/NCBI
8	U.S Department of Health and Human Services FaDA, . October;2011.U.S. Department of Health and Human Services, Food and Drug Administration, October 2011: Guidance for Industry. Clinical Considerations for Therapeutic Cancer Vaccines. 2011.
9	Nagorsen D and Thiel E: Clinical and immunologic responses to active specific cancer vaccines in human colorectal cancer. Clin Cancer Res. 12:3064–3069. 2006. View Article : Google Scholar : PubMed/NCBI
10	Copier J, Whelan M and Dalgleish A: Biomarkers for the development of cancer vaccines: Current status. Mol Diagn Ther. 10:337–343. 2006. View Article : Google Scholar : PubMed/NCBI
11	Whiteside TL: Immune responses to cancer: Are they potential biomarkers of prognosis? Front Oncol. 3:1072013. View Article : Google Scholar : PubMed/NCBI
12	Yagyu R, Furukawa Y, Lin YM, Shimokawa T, Yamamura T and Nakamura Y: A novel oncoprotein RNF43 functions in an autocrine manner in colorectal cancer. Int J Oncol. 25:1343–1348. 2004.PubMed/NCBI
13	Shimokawa T, Matsushima S, Tsunoda T, Tahara H, Nakamura Y and Furukawa Y: Identification of TOMM34, which shows elevated expression in the majority of human colon cancers, as a novel drug target. Int J Oncol. 29:381–386. 2006.PubMed/NCBI
14	Kikuchi T, Daigo Y, Katagiri T, Tsunoda T, Okada K, Kakiuchi S, Zembutsu H, Furukawa Y, Kawamura M, Kobayashi K, et al: Expression profiles of non-small cell lung cancers on cDNA microarrays: Identification of genes for prediction of lymph-node metastasis and sensitivity to anti-cancer drugs. Oncogene. 22:2192–2205. 2003. View Article : Google Scholar : PubMed/NCBI
15	Olofsson B, Korpelainen E, Pepper MS, Mandriota SJ, Aase K, Kumar V, Gunji Y, Jeltsch MM, Shibuya M, Alitalo K and Eriksson U: Vascular endothelial growth factor B (VEGF-B) binds to VEGF receptor-1 and regulates plasminogen activator activity in endothelial cells. Proc Natl Acad Sci USA. 95:pp. 11709–11714. 1998; View Article : Google Scholar : PubMed/NCBI
16	Millauer B, Wizigmann-Voos S, Schnurch H, Martinez R, Møller NP, Risau W and Ullrich A: High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell. 72:835–846. 1993. View Article : Google Scholar : PubMed/NCBI
17	Hazama S, Nakamura Y, Tanaka H, Hirakawa K, Tahara K, Shimizu R, Ozasa H, Etoh R, Sugiura F, Okuno K, et al: A phase II study of five peptides combination with oxaliplatin-based chemotherapy as a first-line therapy for advanced colorectal cancer (FXV study). J Transl Med. 12:1082014. View Article : Google Scholar : PubMed/NCBI
18	Uchida N, Tsunoda T, Wada S, Furukawa Y, Nakamura Y and Tahara H: Ring finger protein 43 as a new target for cancer immunotherapy. Clin Cancer Res. 10:8577–8586. 2004. View Article : Google Scholar : PubMed/NCBI
19	Suda T, Tsunoda T, Daigo Y, Nakamura Y and Tahara H: Identification of human leukocyte antigen-A24-restricted epitope peptides derived from gene products upregulated in lung and esophageal cancers as novel targets for immunotherapy. Cancer Sci. 98:1803–1808. 2007. View Article : Google Scholar : PubMed/NCBI
20	Ishizaki H, Tsunoda T, Wada S, Yamauchi M, Shibuya M and Tahara H: Inhibition of tumor growth with antiangiogenic cancer vaccine using epitope peptides derived from human vascular endothelial growth factor receptor 1. Clin Cancer Res. 12:5841–5849. 2006. View Article : Google Scholar : PubMed/NCBI
21	Wada S, Tsunoda T, Baba T, Primus FJ, Kuwano H, Shibuya M and Tahara H: Rationale for antiangiogenic cancer therapy with vaccination using epitope peptides derived from human vascular endothelial growth factor receptor 2. Cancer Res. 65:4939–4946. 2005. View Article : Google Scholar : PubMed/NCBI
22	Iizuka N, Oka M, Yamada-Okabe H, Nishida M, Maeda Y, Mori N, Takao T, Tamesa T, Tangoku A, Tabuchi H, et al: Oligonucleotide microarray for prediction of early intrahepatic recurrence of hepatocellular carcinoma after curative resection. Lancet. 361:923–929. 2003. View Article : Google Scholar : PubMed/NCBI
23	Boon T and van der Bruggen P: Human tumor antigens recognized by T lymphocytes. J Exp Med. 183:725–729. 1996. View Article : Google Scholar : PubMed/NCBI
24	Okabe H, Satoh S, Kato T, Kitahara O, Yanagawa R, Yamaoka Y, Tsunoda T, Furukawa Y and Nakamura Y: Genome-wide analysis of gene expression in human hepatocellular carcinomas using cDNA microarray: Identification of genes involved in viral carcinogenesis and tumor progression. Cancer Res. 61:2129–2137. 2001.PubMed/NCBI
25	Okuno K, Sugiura F, Itoh K, Yoshida K, Tsunoda T and Nakamura Y: Recent advances in active specific cancer vaccine treatment for colorectal cancer. Curr Pharm Biotechnol. 13:1439–1445. 2012. View Article : Google Scholar : PubMed/NCBI
26	Kijima T, Hazama S, Tsunedomi R, Tanaka H, Takenouchi H, Kanekiyo S, Inoue Y, Nakashima M, Iida M, Sakamoto K, et al: Micro RNA-6826 and −6875 in plasma are valuable non-invasive biomarkers that predict the efficacy of vaccine treatment against metastatic colorectal cancer. Oncol Rep. 37:23–30. 2017.PubMed/NCBI
27	Li X, Shi Y, Yin Z, Xue X and Zhou B: An eight-miRNA signature as a potential biomarker for predicting survival in lung adenocarcinoma. J Transl Med. 12:1592014. View Article : Google Scholar : PubMed/NCBI
28	Lu YC, Chang JT, Liao CT, Kang CJ, Huang SF, Chen IH, Huang CC, Huang YC, Chen WH, Tsai CY, et al: OncomiR-196 promotes an invasive phenotype in oral cancer through the NME4-JNK-TIMP1-MMP signaling pathway. Mol Cancer. 13:2182014. View Article : Google Scholar : PubMed/NCBI
29	Ge J, Chen Z, Li R, Lu T and Xiao G: Upregulation of microRNA-196a and microRNA-196b cooperatively correlate with aggressive progression and unfavorable prognosis in patients with colorectal cancer. Cancer Cell Int. 14:1282014. View Article : Google Scholar : PubMed/NCBI
30	Pan Y, Meng M, Zhang G, Han H and Zhou Q: Oncogenic microRNAs in the genesis of leukemia and lymphoma. Curr Pharm Des. 20:5260–5267. 2014. View Article : Google Scholar : PubMed/NCBI
31	Chen WX, Ren LH and Shi RH: Implication of miRNAs for inflammatory bowel disease treatment: Systematic review. World J Gastrointest Pathophysiol. 5:63–70. 2014.PubMed/NCBI
32	Galon J, Mlecnik B, Bindea G, Angell HK, Berger A, Lagorce C, Lugli A, Zlobec I, Hartmann A, Bifulco C, et al: Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours. J Pathol. 232:199–209. 2014. View Article : Google Scholar : PubMed/NCBI
33	Zhang GJ, Zhou H, Xiao HX, Li Y and Zhou T: MiR-378 is an independent prognostic factor and inhibits cell growth and invasion in colorectal cancer. BMC Cancer. 14:1092014. View Article : Google Scholar : PubMed/NCBI
34	Lee DY, Deng Z, Wang CH and Yang BB: MicroRNA-378 promotes cell survival, tumor growth and angiogenesis by targeting SuFu and Fus-1 expression. Proc Natl Acad Sci USA. 104:pp. 20350–20355. 2007; View Article : Google Scholar : PubMed/NCBI
35	Chen H, Ren C, Han C, Wang D, Chen Y and Fu D: Expression and prognostic value of miR-486-5p in patients with gastric adenocarcinoma. PLoS One. 10:e01193842015. View Article : Google Scholar : PubMed/NCBI
36	Wang J, Tian X, Han R, Zhang X, Wang X, Shen H, Xue L, Liu Y, Yan X, Shen J, et al: Downregulation of miR-486-5p contributes to tumor progression and metastasis by targeting protumorigenic ARHGAP5 in lung cancer. Oncogene. 33:1181–1189. 2014. View Article : Google Scholar : PubMed/NCBI
37	Song L, Lin C, Gong H, Wang C, Liu L, Wu J, Tao S, Hu B, Cheng SY, Li M and Li J: miR-486 sustains NF-κB activity by disrupting multiple NF-κB-negative feedback loops. Cell Res. 23:274–289. 2013. View Article : Google Scholar : PubMed/NCBI
38	Fisher DT, Appenheimer MM and Evans SS: The two faces of IL-6 in the tumor microenvironment. Semin Immunol. 26:38–47. 2014. View Article : Google Scholar : PubMed/NCBI
39	Gajewski TF, Schreiber H and Fu YX: Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol. 14:1014–1022. 2013. View Article : Google Scholar : PubMed/NCBI