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

Background:Long non-coding RNA and mRNAs are long RNAs ({greater than or equal to} 200 nucleotides) compared to microRNAs. In blood, long RNAs may be protected by serum extracellular vesicles, such as apoptotic bodies (ABs), microvesicles (MVs), and exosomes (EXOs). They are potential biomarker for identifying cancer. Methods:Sera from 76 pre-operative CRC patients, 76 age- and sex-matched healthy subjects and 20 colorectal adenoma (CA) patients without CRC were collected. We investigate the distribution of long RNAs the three vesicles. Seventy-nine cancer-related long RNA were chosen and detected using quantitative PCR (qPCR). Results: OThe quantity of long RNA have varying distribution among three subtypes of extracellular vesicles in serum. Most mRNAs and lncRNAs genes had higher quantity in EXOs than that in ABs and MVs, while MVs contain lowest quantity. We investigated 79 long RNAs chosen from the The Cancer Genome Atlas (TCGA) and the LncRNADisease database in the sera of healthy patients, and those with colorectal cancer (CRC). In the training and test sets, the areas under the curves (AUC) 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). Conclusions:The present study shows that exosomal mRNAs and lncRNAs in serum could be used as biomarkers to detect CRC. Impact:Among three types of vesicles in sera, EXOs were the richest reservoir for almost all measured long RNAs. the combination of 2 mRNAs, KRTAP5-4, MAGEA3, and 1 lncRNA, BCAR4 could be potential candidates to detect colorectal cancer.