GENETIC AND EPIGENETIC PREDICTORS OF RECTAL TUMORS RADIOTHERAPY EFFECTIVENESS
The main problem of rectal tumors radiation therapy remains the radioresistance of tumor cells, which leads to a low degree of tumor response to treatment. Over the past 30 years, a number of molecular markers have been proposed as predictors of response to radiation therapy, but none have entered clinical practice. Accordingly, the screening of such markers remains an urgent task, for the solution of which it is necessary to integrate data on various biomarkers types obtained during radiation therapy according to a unified scheme. Therefore, the aim of the study was to screen markers of rectal tumors radioresistance based on data on gene copy number, gene expression and microRNA. The study included 75 patients with diagnosed rectal cancer and 30 apparently healthy donors (without oncological pathology). Radiation therapy was carried out on Novalis TX according to the scheme SFD = 2.4 Gy to TFD = 54 Gy. Expression indicators of genes and microRNA were determined in biopsy samples, copy number in biopsy samples and extracellular DNA by the Real-Time qPCR method. It was shown that the effectiveness of radiation therapy is associated with the differential expression of 13 microRNAs (miRNA-130b, miRNA-1249, miRNA-6820, miRNA-6757, miRNA-1273h, miRNA-6737, miRNA-6819, miRNA-557, miRNA-6874, miRNA-4728, miRNA-6808, miRNA-3202, miRNA-5195), which provides efficient regulation of DNA double-strand break repair system (BRCA2, H2AX and RBBP8) and regulation of apoptosis (CASP9 and BCL2). In turn, the expression of genes targeted by these microRNAs can also act as a marker of sensitivity to radiation therapy. The study confirmed the relationship between gene expression and copy number, which makes it possible to use the copy number of genes CASP-9, BCL-2, BRCA-2, H2AX и RBBP-8 also as predictors of radiation therapy effectiveness in biopsy samples, and the copy number of genes H2AX and RBBP-8 as a marker of radiation therapy effectiveness in cfDNA of rectal cancer patients.