Circulating miRNA expression over the course of colorectal cancer treatment

Oncol Lett. 2022 Jan;23(1):18. doi: 10.3892/ol.2021.13136. Epub 2021 Nov 15.

Abstract

Colorectal cancer (CRC) is the third-most common cancer type in males and the second-most common cancer type in females, and has the second-highest overall mortality rate worldwide. Approximately 50% of patients in stage I-III develop metastases, mostly localized to the liver. All physiological conditions occurring in the organism are also reflected in the levels of circulating microRNAs (miRNAs/miRs) in patients. miRNAs are a class of small, non-coding, single-stranded RNAs consisting of 18-25 nucleotides, which have important roles in various cellular processes. The aim of the present study was to evaluate a panel of seven circulating miRNAs (miR-106a-5p, miR-210-5p, miR-155-5p, miR-21-5p, miR-103a-3p, miR-191-5p and miR-16-5p) as biomarkers for monitoring patients undergoing adjuvant treatment of CRC. Total RNA was extracted from the plasma of patients with CRC prior to surgery, in the early post-operative period (n=60) and 3 months after surgery (n=14). The levels of the selected circulating miRNAs were measured with the miRCURY LNA miRNA PCR system and fold changes were calculated using the standard ∆∆Cq method. DIANA-miRPath analysis was used to evaluate the role of significantly deregulated miRNAs. The results indicated significant upregulation of miR-155-5p, miR-21-5p and miR-191-5p, and downregulation of miR-16-5p directly after the surgery. In paired follow-up samples, the most significant upregulation was detected for miR-106a-5p and miR-16-5p, and the most significant downregulation was for miR-21-5p. Pathway analysis outlined the role of the differentially expressed miRNAs in cancer development, but the same pathways are also involved in wound healing and regeneration of intestinal epithelium. It may be suggested that these processes should also be considered in studies investigating sensitive and easily detectable circulating biomarkers for recurrence in patients.

Keywords: colorectal cancer; intestinal wound healing; miRNA expression; pathway analysis.

Grants and funding

This study was supported by the Project of Slovak Research and Development Agency (grant no. APVV-16-0066) as well as by a grant from The Ministry of Education, Science, Research and Sport of the Slovak Republic (grant no. VEGA-1/0380/18) and by the Operational Programme Integrated Infrastructure for the project ‘Integrative strategy in development of personalized medicine of selected malignant tumours and its impact on quality of life’ (grant no. IMTS: 313011V446), co-financed by the European Regional Development Fund.