Extensive screening of microRNA populations identifies hsa-miR-375 and hsa-miR-133a-3 p as selective markers for human rectal and colon cancer

MicroRNAs (miRNAs) are ˜22-nt molecules exerting control of protein expression in cancer tissues. The current study determined the full spectrum of miRNA dysregulation in freshly isolated human colon or rectal cancer biopsies as well as in controls of healthy adjacent tissue (total of n = 100) using an Illumina sequencing technology. In this work, we aimed to identify miRNAs that may serve as future marker to discern between these two subtypes. DESeq2 analysis revealed 53 significantly dysregulated miRNAs in colon cancer, 67 miRNAs in rectal cancer, and 97 miRNAs in both at a P_adj value < 0.05 and ≥10 read counts. 65% of miRNAs were upregulated in colon as well as rectal cancer. Highest significant dysregulation (P_adj < 0.00001) was detected for hsa-miR-21 – 5 p, -215 – 5 p and -378a in both colon and rectal cancer. Among the group of miRNAs with P_adj < 0.05 and more than 2-fold expression differences, hsa-miR-375 was detected in rectal cancer only, and hsa-miR-133a-3 p only in colon cancer. Receiver operating characteristic (ROC) analysis confirmed highly distinct sensitivities for hsa-miR-375 to detect rectal cancer (area under the curve (AUC): 0.9), while hsa-miR-133a-3 p (AUC: 0.89) had the highest sensitivity for detecting colon cancer. We conclude that hsa-miR-375 and hsa-miR-133a-3 p may serve as new markers of rectal or colon cancer and should be further investigated to search for different etiologies of CRC.