MiRNAs-Based Molecular Signature for KRAS Mutated and Wild Type Colorectal Cancer: An Explorative Study.

Elena Milanesi,Gabriel Becheanu,Alessandro Salvi,Giuseppina De Petro,Vlad Herlea,Teodora Ecaterina Manuc,Alina Ioana Bucuroiu,Mircea Manuc,Maria Dobre

doi:10.1155/2020/4927120

Abstract

microRNAs (miRNAs) have been proposed as promising molecular biomarkers for diagnosis, prognosis, and responsive therapeutic targets in different types of cancer, including colorectal cancer (CRC). In this study, we evaluated the expression levels of 84 cancer-associated miRNAs in a cohort of 39 human samples comprising 13 peritumoral and 26 tumoral tissues from surgical specimens of CRC patients. KRAS mutations were detected in 11 tumoral samples. In a first analysis, we found 5 miRNAs (miR-215-5p, miR-9-5p, miR-138-5p, miR378a-3p, and miR-150-5p) that were significantly downregulated and one upregulated (miR-135b-5p) in tumoral tissues compared with the peritumoral tissues. Furthermore, by comparing miRNA profile between KRAS mutated CRC tissues respect to wild type CRC tissues, we found 7 miRNA (miR-27b-3p, miR-191-5p, miR-let7d-5p, miR-15b-5p, miR-98-5p, miR-10a-5p, and miR-149-5p) downregulated in KRAS mutated condition. In conclusion, we have identified a panel of miRNAs that specifically distinguish CRC tissues from peritumoral tissue and a different set of miRNAs specific for CRC with KRAS mutations. These findings may contribute to the discovering of new molecular biomarkers with clinic relevance and might shed light on novel molecular aspects of CRC.

Highlights

According to GLOBOCAN 2018 (Global Cancer Observatory), colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide and the fourth most incident cancer in the world, with a higher incidence among men [1]
The results showed that miR-215-5p was significantly downregulated in the small group (FR = −2:87, p = 0:003). miR-9-5p, Table 2: miRNAs differentially expressed in tumoral (n = 26) vs peritumoral (n = 13) tissues. miRNAs are ordered to increasing fold regulation
We further stratified the tumoral tissues according to the presence (T_M) or lack (T_WT) of KRAS mutations, and we compared the miRNAs profile of the two groups to assess the miRNAs differentially expressed in CRC mutated respect to CRC wild type

Summary

Introduction

According to GLOBOCAN 2018 (Global Cancer Observatory), colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide and the fourth most incident cancer in the world, with a higher incidence among men [1]. 70-80% of cases of CRC occur sporadically and depend on risk factors that include history ulcerative colitis and Crohn’s disease [2], and constellation of modifiable environmental factors, more frequent in western countries, which include obesity, physical inactivity, poor diets, alcohol drinking, and smoking [3]. Three canonical major distinct genetic pathways have been attributed to the development of sporadic CRC. These are not mutually exclusive and include the chromosomal instability pathway (CIN), the microsatellite instability pathway (MSI), and the CpG island methylator phenotype pathway (CIMP) [7]. The CIN pathway is the most frequent; it involves the classic adenoma-carcinoma sequence and genetic alterations in adenomatous polyposis coli—APC—(30–70%)

Methods

Results

Discussion

Conclusion