Circulating Long RNAs in Serum Extracellular Vesicles: Their Characterization and Potential Application as Biomarkers for Diagnosis of Colorectal Cancer

Cancer Epidemiol Biomarkers Prev. 2016 Jul;25(7):1158-66. doi: 10.1158/1055-9965.EPI-16-0006. Epub 2016 May 18.


Background: Long noncoding RNA (lncRNA) and mRNAs are long RNAs (≥200 nucleotides) compared with miRNAs. In blood, long RNAs may be protected by serum extracellular vesicles, such as apoptotic bodies (AB), microvesicles (MV), and exosomes (EXO). They are potential biomarkers for identifying cancer.

Methods: Sera from 76 preoperative colorectal cancer patients, 76 age- and sex-matched healthy subjects, and 20 colorectal adenoma patients without colorectal cancer were collected. We investigated the distribution of long RNAs into the three vesicles. Seventy-nine cancer-related long RNAs were chosen and detected using qPCR.

Results: The quantity of long RNA has varying distribution among three subtypes of extracellular vesicles in serum. Most mRNA and lncRNA genes had higher quantity in EXOs than that in ABs and MVs, whereas MVs contain lowest quantity. We investigated 79 long RNAs chosen from The Cancer Genome Atlas and the LncRNADisease database in the sera of healthy patients, and those with colorectal cancer. In the training and test sets, the AUCs were 0.936 and 0.877, respectively. The AUC of total serum RNA was lower (0.857) than that of exosomal RNA in the same samples (0.936).

Conclusion: The present study shows that exosomal mRNAs and lncRNAs in serum could be used as biomarkers to detect colorectal cancer.

Impact: Among three types of vesicles in sera, EXOs were the richest reservoir for almost all measured long RNAs. The combination of two mRNAs, KRTAP5-4 and MAGEA3, and one lncRNA, BCAR4, could be potential candidates to detect colorectal cancer. Cancer Epidemiol Biomarkers Prev; 25(7); 1158-66. ©2016 AACR.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Case-Control Studies
  • Cohort Studies
  • Colorectal Neoplasms / blood*
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / genetics
  • Exosomes / metabolism
  • Extracellular Vesicles / genetics*
  • Female
  • Humans
  • Male
  • Middle Aged
  • RNA, Long Noncoding / blood*
  • RNA, Long Noncoding / genetics
  • RNA, Messenger / blood*
  • RNA, Messenger / genetics
  • Sensitivity and Specificity


  • Biomarkers, Tumor
  • RNA, Long Noncoding
  • RNA, Messenger