The features of KRAS gene transcriptional activity and significance in colorectal cancer
Colorectal adenocarcinoma (CRA) is the result of numerous mutations accumulation. The aim of the work was to study KRAS gene transcriptional activity at I, II, III, and IV stages of CRA development and to analyze the correlations between KRAS and Ki-67, TP53, CDH1, CTNNB1 genes transcriptional activity. Pathohistological and molecular-genetic study of surgical material from 40 patients with CRA, as well as sectional material of 10 fragments of the distal colonic wall was conducted. The following statistical methods were used: descriptive statistics, χ2 test, Kruskal-Wallis test, Spearman’s rank correlation coefficient. It was established that CRA is characterized by increased KRAS transcriptional activity: Me of mRNA expression is 0.42 (0.36; 0.43) at stage I, 1.31 (1.09; 2.91) at stage II, 1.75 (1.31; 2.93) at stage III, and 2.91 (1.85; 3.50) at stage IV. Decreasing of Ki-67 gene transcriptional activity was revealed: Me of mRNA expression is 3.20 (2.31; 3.59) at stage I, 2.92 (1.80; 3.50) at stage II, 1,27 (1.19; 2.08) at stage III, and 0.52 (0.28; 1.04) at stage IV. As about TP53 gene, increasing of transcriptional activity was detected: Me is 2.15 (0.82; 2.30) at stage I, 2.80 (1.32; 4.50) at stage II, 3.80 (2.32; 6.50) at stage III, 7.80 (5.99; 8.92) at stage IV. Also, a direct medium correlation between the KRAS and TP53 transcriptional activity levels was revealed. There is a decreasing of CDH1 transcriptional activity: Me is 0.88 (0.42; 1.14) at stage I, 0.48 (0.23; 1.13) at stage II, 0.15 (0.09; 0.36) at stage III and 0.08 (0.04; 0.41) at stage IV. A reverse medium correlation between KRAS and CDH1 was revealed. The study of CTNNB1 gene mRNA at different stages of CRA indicated the absence of statistically significant difference: Me is 2.88 (2.38; 5.38) at stage I, 3.83 (2.59; 5.99) at stage II, 2.02 (1.38; 6.95) at stage III, and 2.27 (1.23; 2.93) at stage IV. So, KRAS gene transcriptional activity increases from I to IV stages in CRA, affecting apoptosis and adhesive properties of cancer cells.
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