Exosomal long noncoding RNA CRNDE-h as a novel serum-based biomarker for diagnosis and prognosis of colorectal cancer
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Tong Liu1,*, Xin Zhang1,*, Shanyu Gao2, Fangmiao Jing3, Yongmei Yang1, Lutao Du1, Guixi Zheng1, Peilong Li1, Chen Li1, Chuanxin Wang1
1Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, People’s Republic of China
2Department of Anorectal Surgery, Shandong Provincial Traditional Chinese Medical Hospital, Jinan, People’s Republic of China
3Oncology Center, Qilu Hospital, Shandong University, Jinan, People’s Republic of China
*These authors have contributed equally to this work
Chuanxin Wang, email: [email protected]
Keywords: exosome, long noncoding RNA, CRNDE-h, colorectal cancer, biomarker
Received: August 02, 2016 Accepted: October 27, 2016 Published: November 19, 2016
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.
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