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.
Highlights
Colorectal cancer (CRC) is one of the most frequent malignant tumors worldwide, with an estimated 1.2 million new cases and 608,700 deaths annually[1]
No significant differences in the expression of exosomal GAPDH and UBC mRNA were found among the five different groups by using Reverse transcriptase quantitative real-time PCR (RT-qPCR) (Figure 2B), indicating that both genes expressed at a constant level in exosomes of serum
Our results indicated that this amplified product was long non-coding RNAs (lncRNAs) Colorectal neoplasia differentially expressed - h (CRNDE-h) isoform, not others (Supplementary Figure S1)
Summary
Colorectal cancer (CRC) is one of the most frequent malignant tumors worldwide, with an estimated 1.2 million new cases and 608,700 deaths annually[1]. Early diagnosis and early treatment can significantly elevate the overall survival rate of CRC patients [2]. Colonoscopy examination can provide high diagnostic accuracy, but it is inconvenient and invasive and may give rise to additional complications, which limits it to the second-level investigation. Biomarkers in plasma and serum perform an important capacity to diagnose cancers. In the currently blood test, the best biomarker carcinoembryonic antigen (CEA) exhibited low sensitivity and specificity, in the early stage of cancer. Novel and reliable CRC-specific biomarkers that can complement and improve the current CRC diagnostic strategies are urgently needed
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