Identification of metastasis-associated microRNAs in serum from rectal cancer patients

// Robin Mjelle 1 , Kjersti Sellaeg 1 , Pal Saetrom 1, 2 , Liv Thommesen 3 , Wenche Sjursen 1, 4 and Eva Hofsli 1, 5 1 Department of Clinical and Molecular Medicine, NO-7491 Trondheim, Norway 2 Department of Computer Science, Norwegian University of Science and Technology, NO-7491 Trondheim, Norway 3 Department of Biomedical Science, Norwegian University of Science and Technology, 7030 Trondheim Norway 4 Department of Medical Genetics, St. Olavs Hospital, Norwegian University of Science and Technology, 7030 Trondheim Norway 5 The Cancer Clinic, St. Olavs Hospital, Trondheim University Hospital, 7030 Trondheim, Norway Correspondence to: Robin Mjelle, email: robin.mjelle@ntnu.no Eva Hofsli, email: eva.hofsli@stolav.no Keywords: rectal cancer, biomarker, microRNA, serum, isomiR Received: January 20, 2017      Accepted: August 31, 2017      Published: September 30, 2017 ABSTRACT MicroRNAs (miRNAs) are promising prognostic and diagnostic biomarkers due to their high stability in blood. Here we investigate the expression of miRNAs and other noncoding (nc) RNAs in serum of rectal cancer patients. Serum from 96 rectal cancer patients was profiled using small RNA sequencing and expression of small RNAs was correlated with the clinicopathological characteristics of the patients. Multiple classes of RNAs were detected, including miRNAs and fragments of tRNAs, snoRNAs, long ncRNAs, and other classes of RNAs. Several miRNAs, miRNA variants (isomiRs) and other ncRNAs were differentially expressed between Stage IV and Stage I-III rectal cancer patients, including several members of the miR-320 family. Furthermore, we show that high expression of miR-320d as well as one tRNA fragment is associated with poor survival. We also show that several miRNAs and isomiRs are differentially expressed between patients receiving preoperative chemoradiotherapy and patients who did not receive any treatment before serum collection. In summary, our study shows that the expression of miRNAs and other small ncRNAs in serum may be used to predict distant metastasis and survival in rectal cancer.