Influence of DNA copy number aberrations and changes in the expression level of homologous recombination genes on the survival of primary operable non-small cell lung cancer patients

Understanding the molecular mechanisms underlying the pathogenesis of lung cancer is critical for developing effective therapeutic strategies. It is important to study the role of key DNA repair genes, such as BRCA1, CHEK1, etc., in the context of the presence of aberrations in them and their influence on long-term treatment outcomes.

Thus, the aim of the work was to assess the presence of chromosomal aberrations and expression in the main genes of the homologous recombination system in lung tumor.

Materials and methods. The study included 111 patients with non-small cell lung cancer (NSCLC) stage IIA-IIIB. RNA and DNA were isolated from the surgical material of normal and tumor tissue. The expression level of HR genes was assessed using RTPCR. The presence of chromosomal aberrations and loss of heterozygosity sites was determined using microarray analysis.

Results. Evaluation of the expression level showed that the presence of hyperexpression (more than 1) of the RAD51D gene is associated with 100 % metastasis-free survival (MFS) compared to the group with low expression (67.5 %), log-rank test p = 0.05. The effect of amplification in the ATM, BRIP1, BRCA1 genes on the increase in their expression was established (at p < 0.05). For the BRCA1 gene, an association was established between the presence of a deletion and gene hypoexpression (p = 0.00006). According to Kaplan – Meier curves, in the presence of amplifications in the PPP2R2A gene in the tumor, the 5-year survival rate is only 50 %, compared to normal copy number with 85 % survival (p = 0.02). The opposite picture is observed for the BRCA2 gene: with a deletion, the survival rate is 54 % versus 88 % in the norm (p = 0.001).

Conclusion. It remains important to further research to better understand the interaction between aberrations in the genes of the HR system and the assessment of the expression profile of these genes and therapeutic responses, which may ultimately lead to more effective and individualized treatment strategies for NSCLC.

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