Cancer-secreted long non-coding RNAs (lncRNAs) are emerging mediators of cancer-host cross talk. Researchers at Shandong University aimed 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:
- 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;
- The stability of exosomal CRNDE-h was evaluated systematically;
- The origin of exosomal CRNDE-h was explorated in vitro and in vivo;
- The diagnostic and prognostic value of exosomal CRNDE-h for CRC were validated in 468 patients.
In the pilot study, the 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.
Quantitative analyses of exosomal CRNDE-h in validation phase
Relative expression of exosomal CRNDE-h in NC (n=80), HP (n=80), IBD (n=80), adenoma (Ad; n=80), and CRC (n=148). Yellow line represents the optimal cut-off value as 0.020 for discriminating CRC from colorectal benign disease groups and normal colonoscopy. Red line represents the median value and the gray line means the 25% and 75% interquartile range. **P<0.001.