title: Exosomal long noncoding RNA CRNDE-h as a novel serum-based biomarker for diagnosis and prognosis of colorectal cancer.
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.
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, People's Republic of China.
authors.forename: Tong
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Anorectal Surgery, Shandong Provincial Traditional Chinese Medical Hospital, Jinan, People's Republic of China.
authors.forename: Shanyu
authors.initials: S
authors.lastname: Gao
authors.affiliation: Oncology Center, Qilu Hospital, Shandong University, Jinan, People's Republic of China.
authors.forename: Fangmiao
authors.initials: F
authors.lastname: Jing
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, People's Republic of China.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, People's Republic of China.
authors.forename: Lutao
authors.initials: L
authors.lastname: Du
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, People's Republic of China.
authors.forename: Guixi
authors.initials: G
authors.lastname: Zheng
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, People's Republic of China.
authors.forename: Peilong
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, People's Republic of China.
authors.forename: Chuanxin
authors.initials: C
authors.lastname: Wang
mesh_terms: D000818:Animals; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D016022:Case-Control Studies; D000073888:Cell-Free Nucleic Acids / Q000097:blood* / Q000235:genetics; D015179:Colorectal Neoplasms / Q000097:blood* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D055354:Exosomes / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D020871:RNA Stability; D062085:RNA, Long Noncoding / Q000097:blood* / Q000235:genetics; D012372:ROC Curve; D015203:Reproducibility of Results; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C586983:CRNDE RNA, human; D000073888:Cell-Free Nucleic Acids; D062085:RNA, Long Noncoding
keywords: CRNDE-h; biomarker; colorectal cancer; exosome; long noncoding RNA