Analysis of exosomal mRNA profile in cancer tissue from patients with colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignant tumors. Exosomes are key modulators of intercellular communication and important participants in CRC tumorigenesis. However, the influence and underlying mechanism of cancer-secreted exosomes in CRC are not fully understood. In the present study, exosome-enriched extracellular vesicles (EVs) were isolated from paired CRC and adjacent normal control tissue (NC) from patients with CRC using ultracentrifugation, size exclusion chromatography and ultrafiltration. Bowtie software was used to identify mRNA expression patterns. Further analyses included functional enrichment analysis using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes for differentially expressed genes (DEGs) and Gene Set Enrichment Analysis for functional enrichment of the entire transcriptome. Gene Set Variation Analysis was used to identify differentially enriched functions and pathways for each sample. Weighted gene correlation network analysis was used to select candidate key genes. The diagnostic performance of the candidate key genes was validated using the models of multiple logistic regression and a support vector machine with the external CRC exosomal RNA database exoRBase. A total of 814 DEGs were identified in the exosome-enriched EVs from patients with CRC compared with those from NC group. The enriched functions were potentially associated with key steps and pathways involved in CRC tumorigenesis, including cell cycle, DNA replication, RNA activity, protein metabolism and the PI3K/Akt', Wnt, MAPK and KRAS pathways, as well as the regulation of mitochondria, the pentose phosphate pathway and intestinal immunity. A total 14 candidate key genes, namely, p53 effector related to PMP-22, MYC, dyskerin pseudouridine synthase 1), VDAC1 (voltage dependent anion channel 1), adenosylhomocysteinase), TMEM123 (transmembrane protein 123), RPL36A (ribosomal protein L36a), CCT5 (chaperonin containing TCP1 subunit 5), CHCHD2 (coiled-coil-helix-coiled-coil-helix domain containing 2), RPS21 (ribosomal protein S21), KRT18 (keratin 18), TGFBI (transforming growth factor beta induced), ETS2 (ETS proto-oncogene 2) and AXIN2 (axin 2), were identified. The present exploratory study revealed pronounced transcriptomic changes in exosome-enriched EV derived from CRC compared with those derived from paracancerous tissue, and may provide a novel platform for understanding tumor microenvironment interactions.