Clinical significance of HRAS and KRAS genes expression in patients with non–small-cell lung cancer.

Abstract Background: The RAS family protooncogenes, including KRAS, NRAS and HRAS, encode proteins responsible for the regulation of growth, differentiation and survival of many cell types. The HRAS and KRAS oncogene mutations are well defined, however, the clinical significance of RAS expressions in non–small-cell lung cancer (NSCLC) is still uncertain. Methods: A total of 39 whole blood samples of NSCLC (the investigated group), collected at three points of time: at the time of diagnosis, 100 days and one year after the surgery, were included in this study. HRAS and KRAS genes mRNA expression were assessed using quantitative real time‑polymerase chain reaction techniques. Results: Increased relative HRAS mRNA levels were found significantly more frequently in the group of smokers (p=0.008). Patients with squamous cell carcinoma subtypes of NSCLC were more likely to show an overexpression of HRAS gene, but not statistically significant (p=0.065). The median overall survival was significantly better in the group with a higher HRAS gene expression (p=0.012). No statistically significant associations were found for the expression of KRAS with any clinicopathological parameters within the study. There were no differences between the relative HRAS and KRAS genes expression levels in blood samples taken from the same patients during the 3 observation points.Conclusion: The potential associations between high HRAS levels, smoking status and histological type of cancer as well as overall survival were observed, which emphasizes the need for further study of the RAS family. Therefore, subsequent research involving larger numbers of patients and a longer follow-up, as well as multicenter study are necessary to confirm our findings.