Sluzhev , M. I., Zaraiskii, M. I., Semiglazov, V. V., Semiglazova, T. Y., Tkachenko, E. V., Kondratev, S. V., Brish, N. A., Alekseeva, Y. V., Abasova, S. V., Kozyukalov, A. S., Petrik, I. V., & Sidorova, A. N. (2024). Threshold Expression Levels of Tumor Control Genes and microRNAs in Tumor and Healthy Tissue of Colorectal Cancer Patients. Voprosy Onkologii, 70(4), 696–706. https://doi.org/10.37469/0507-3758-2024-70-4-696-706

Abstract

Introduction. Tumor control genes and miRNAs play an important role in the tumor process in colorectal cancer (CRC). The expression of these genes differs in tumor and healthy tissues. There is no data on threshold levels of gene expression in tumors and healthy tissues at different distances.

Aim. The purpose of the study is to determine the threshold levels of expression of tumor control genes (E2F1, E2F3, TGFB, NFKB, KLF-12, EGFR and MMP9) and miRNAs (miRNA-15, -16, -21, -34, -126, -128, - 210 and - 342) in tumor and healthy tissues at distances of 5 and 10 cm from the tumor in CRC patients.

Materials and Methods. The study included 10 patients with colorectal cancer. Diagnosis was made by sigmoidoscopy or colonoscopy with biopsy of tumor and healthy tissue at a distance of 5 cm and 10 cm from the tumor. The samples were tested for the expression levels of tumor control genes. (E2F1, E2F3, TGFB, NFKB, KLF-12, EGFR and MMP9) and miRNAs (miRNA-15, -16, -21, -34, -126, -128, -210 and - 342).

Results. The threshold expression level of the miRNA-21 gene was determined to be 7.21 REU with a sensitivity of 90 % and specificity 89.5 % (p = 0.00004); the threshold level of expression of the miRNA-342 gene was equal to 16.04 REU with a sensitivity of 90 % and a specificity of 84.2 % (p = 0.00027); threshold level of E2F3 gene expression was equal to 0.380 REU with a sensitivity of 80 % and specificity of 68.4 % (p = 0.031); threshold level of NFkB gene expression was equal to 0.243 REU with a sensitivity of 70 % and specificity of 78.9 % (p = 0.022). It was found that the larger the tumor size, the lower the expression level of the miRNA-21 and miRNA-342 genes (r = –0.991, p = 0.000015 and r = –0.908, p = 0.005 respectively).

Conclusion. Threshold levels in the expression of the E2F3, miRNA-21, miRNA-342 and NFKB genes were identified. Increased levels of miR-21 and decreased levels of miR-342 in healthy tissue may be a factor in carcinogenesis and a predictor of local relapse and progression. These data can be used in clinical studies assessing the prognostic and predictive role of gene expression.

https://doi.org/10.37469/0507-3758-2024-70-4-696-706

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