Abstract 2130: Association between miR-18a-3p, miR-143 and expression of the wild-type KRAS gene in patients with sporadic colorectal cancer

Abstract

Abstract Introduction: Colorectal cancer (CRC) has the third-highest incidence and the fourth-highest mortality from cancer globally. In the genesis of CRC, mutations have been identified in the KRAS gene associated with prognosis and therapeutic management, however, the epigenetic mechanisms that modulate the expression of KRAS in CRC patients when there are no mutations in the gene are not well known. miR-18a-3p and miR-143 have been described to target KRAS and thus may regulate gene expression. Objective: To determine if there is a relationship between the expression of the wild-type KRAS gene (mRNA and protein) and the expression levels of miR-143 and miR-18a-3p in FFPE tissue samples from CRC patients. Methodology: RNA was extracted from FFPE tumor tissue samples from 51 cases of patients with CRC. Expression of wild-type KRAS mRNA, miR-143 and miR-18a-3p was evaluated by qRT-PCR and expression levels of KRAS protein by immunohistochemistry. Contingency tables, Pearson's Chi-square test and logistic regression analysis were used for data analysis. Results: Regarding the expression levels of wild-type KRAS protein, a higher number of cases with a cytoplasmic expression of the protein was identified (98%) compared to the expression in the cell membrane (31%). In 7,8% (4/51) of the cases, it was not possible to determine the mRNA expression of the KRAS gene, while in 21,3% (10/47) no expression was detected. In 78,7% of the cases in which KRAS mRNA expression was detected, low (40,4%; 19/47) and high (38,3%; 18/47) expression were categorized according to the results found. It was not evidenced by a correlation between protein expression levels and mRNA expression levels of the wild-type KRAS gene. When determining the expression levels of miR-18a-3p and miR-143, it was found that 64,7% (33/51) of cases had an absent expression of miR-18a-3p and 54,9% (28/51) of cases had an absent or very low expression for miR-143. By means of a logistic regression analysis adjusted by age, stage, sex and presence or absence of KRAS protein in the membrane, it was determined that the presence of miR-18a-3p is inversely related to KRAS mRNA levels significantly (p=0,048; OR=0,346) while miR-143 only shows a tendency to an inverse correlation with KRAS mRNA levels (p=0,119; OR=0,469). Conclusions: No correlation was found between mRNA and protein expression levels of the wild-type KRAS gene, suggesting that protein levels do not strictly depend on mRNA levels. A significant inverse association was found between miR-18a-3p and wild-type KRAS mRNA levels. Citation Format: Jehison-Alirio Herrera-Pulido, Orlando Ricaurte Guerrero, Jinneth Acosta Forero, Gustavo Hernández Suárez, Pablo Moreno-Acosta, María-Carolina Sanabria Salas, Humberto Arboleda Granados, Alfredo Romero Rojas, Martha Lucía Serrano López. Association between miR-18a-3p, miR-143 and expression of the wild-type KRAS gene in patients with sporadic colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2130.