Exosomal long noncoding RNA CRNDE-h as a novel serum-based biomarker for diagnosis and prognosis of colorectal cancer

Abstract

// Tong Liu 1, * , Xin Zhang 1, * , Shanyu Gao 2 , Fangmiao Jing 3 , Yongmei Yang 1 , Lutao Du 1 , Guixi Zheng 1 , Peilong Li 1 , Chen Li 1 , Chuanxin Wang 1 1 Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, People’s Republic of China 2 Department of Anorectal Surgery, Shandong Provincial Traditional Chinese Medical Hospital, Jinan, People’s Republic of China 3 Oncology Center, Qilu Hospital, Shandong University, Jinan, People’s Republic of China * These authors have contributed equally to this work Correspondence to: Chuanxin Wang, email: cxwang@sdu.edu.cn Keywords: exosome, long noncoding RNA, CRNDE-h, colorectal cancer, biomarker Received: August 02, 2016      Accepted: October 27, 2016      Published: November 19, 2016 ABSTRACT Cancer-secreted long non-coding RNAs (lncRNAs) are emerging mediators of cancer-host cross talk. The aim of our study was to illustrate the clinical significance of the lncRNA CRNDE-h in exosomes purified from the serum of patients with colorectal cancer (CRC). The study was divided into four parts: (1) The exosome isolated methods and lncRNA detected methods which accurately and reproducibly measure CRC-related exosomal CRNDE-h in serum were optimized in preliminary pilot stage; (2) The stability of exosomal CRNDE-h was evaluated systematically; (3) The origin of exosomal CRNDE-h was explorated in vitro and in vivo ; (4) The diagnostic and prognostic value of exosomal CRNDE-h for CRC were validated in 468 patients. In pilot study, our results indicated that exosomal CRNDE-h was detectable and stable in serum of CRC patients, and derived from tumor cells. Then, the increased expression of exosomal CRNDE-h was successfully validated in 148 CRC patients when compared with colorectal benign disease patients and healthy donors. Exosomal CRNDE-h level significantly correlated with CRC regional lymph node metastasis ( P = 0.019) and distant metastasis ( P = 0.003). Moreover, at the cut-off value of 0.020 exosomal CRNDE-h level of serum, the area under ROC curve distinguishing CRC from colorectal benign disease patients and healthy donors was 0.892, with 70.3% sensitivity and 94.4% specificity, which was superior to carcinoembryogenic antigen. In addition, high exosomal CRNDE-h level has a lower overall survival rates than that for low groups (34.6% vs. 68.2%, P < 0.001). In conclusion, detection of lncRNA CRNDE-h in exosome shed a light on utilizing exosomal CRNDE-h as a noninvasive serum-based tumor marker for diagnosis and prognosis of CRC.