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

• Published in: Oncotarget Vol. 7; no. 51; pp. 85551 - 85563
• Main Authors: Liu, Tong, Zhang, Xin, Gao, Shanyu, Jing, Fangmiao, Yang, Yongmei, Du, Lutao, Zheng, Guixi, Li, Peilong, Li, Chen, Wang, Chuanxin
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 20.12.2016
• Subjects: Animals; Area Under Curve; Biomarkers, Tumor - biosynthesis; Biomarkers, Tumor - genetics; Case-Control Studies; Cell-Free Nucleic Acids - blood; Cell-Free Nucleic Acids - genetics; Colorectal Neoplasms - blood; Colorectal Neoplasms - genetics; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Exosomes - genetics; Exosomes - metabolism; Exosomes - pathology; Female; HCT116 Cells; HT29 Cells; Humans; Kaplan-Meier Estimate; Male; Mice, Inbred BALB C; Mice, Nude; Middle Aged; Pilot Projects; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Reproducibility of Results; Research Paper; RNA Stability; RNA, Long Noncoding - blood; RNA, Long Noncoding - genetics; ROC Curve; Up-Regulation; long noncoding RNA; CRNDE-h; colorectal cancer; biomarker; exosome
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.13465

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.