Exosome-encapsulated microRNAs as circulating biomarkers for colorectal cancer

// Shushan Yan 1, 2, * , Bing Han 3, * , Shunyuan Gao 4, * , Xiaochen Wang 1 , Zengfang Wang 5 , Fakai Wang 6 , Jianjun Zhang 7 , Donghua Xu 8, 9 and Beicheng Sun 1 1 Key Laboratory on Living Donor Liver Transplantation, Ministry of Health, Department of Liver Surgery, Collaborative Innovation Center For Cancer Personalized Medicine, First Affiliated Hospital of Nanjing Medical University, Nanjing, China 2 Department of Gastrointestinal and Anal Diseases Surgery, The Affiliated Hospital of Weifang Medical University, Weifang, China 3 Department of Clinical Laboratory, People’s Hospital of Zoucheng, Zoucheng, China 4 Department of Neurology, The Affiliated Huai’an Hospital of Xuzhou Medical University and The Second People’s Hospital of Huai’an, Huai’an, China 5 Department of Gynecology and Obstetrics, Weifang Hospital of Maternal and Child Health, Weifang, China 6 Department of Neurosurgery, The Affiliated Hospital of Weifang Medical University, Weifang, China 7 Department of Obstetrics, The Affiliated Hospital of Weifang Medical University, Weifang, China 8 Department of Rheumatology and Immunology, The Affiliated Hospital of Weifang Medical University, Weifang, China 9 Clinical Medicine College, Weifang Medical University, Weifang, China * These authors contributed equally to this work Correspondence to: Beicheng Sun, email: sunbc@njmu.edu.cn Donghua Xu, email: flower322@163.com Jianjun Zhang, email: zhjianjun567@163.com Keywords: exosomes, microRNAs, colorectal cancer Received: March 02, 2017      Accepted: June 08, 2017      Published: June 16, 2017 ABSTRACT Currently available studies have suggested that a number of exosome-encapsulated microRNAs (miRNAs) are recognized as stable biomarkers for cancers. However, little is known about the effect of exosomal miRNAs on colorectal cancer (CRC). The aim of study is to identify specific miRNAs in serum exosomes, which may serve as potential diagnostic and prognostic biomarkers and therapeutic targets for CRC. Microarray analyses of miRNAs in serum exosomes from 3 primary CRC patients and 3 healthy controls were performed. Those differentially expressed exosome-encapsulated miRNAs were verified in exosome-enriched serum samples from 77 CRC patients and 20 healthy controls by quantitative real-time PCR (qRT-PCR). A total of 39 aberrantly expressed miRNAs in serum exosomes were identified by microarray analysis. After confirmation by qRT-PCR, we found that 5 exosome-encapsulated miRNAs (miR-638, miR-5787, miR-8075, miR-6869-5p and miR-548c-5p) were significantly down-regulated, while 2 exosome-encapsulated miRNAs (miR-486-5p and miR-3180-5p) were significantly up-regulated in serum. Decreased levels of miR-638 in serum exosomes were associated with increased risk of liver metastasis and later TNM stage of CRC. Networks analyses revealed that 5 aberrantly expressed miRNAs (miR-638, miR-5787, miR-8075, miR-6869-5p, and miR-548c-5p) might be involved in the process of glucose metabolism in CRC. The present study shows the specific serum profile of exosome-encapsulated miRNAs in CRC. Those specific miRNAs in serum exosomes may serve as disease biomarkers and novel therapeutic targets for CRC.