Comprehensive Analysis of the Expression and Clinical Significance of RAS Family Members in Non-Small Cell Lung Cancer Based on Bioinformatics Data and the A549 Cell Line Model

Abstract

Lung cancer is the second most frequent worldwide diagnosed cancer. Mutations in the RAS genes family are among the most common oncogenic alterations occurring in non-small cell lung cancer (NSCLC). Many treatment options against KRAS mutations have been developed for NSCLC; however, they remain insufficient. Moreover, the role of KRAS and HRAS gene expression in lung cancer remains unclear. However, inhibitors of RAS genes expression seem to be a good candidate for new drugs agents in NSCLC. This study used bioinformatical analysis to determine KRAS and HRAS gene expression and its clinical significance, and then examined the influence of three different RAS inhibitors (farnesythiosalicylic acid (FTS), deltarasin and Kobe0065) on cell growth and the KRAS and HRAS gene expression (by RT-qPCR) in human NSCLC A549 cells. KRAS and HRAS were shown to be overexpressed in NSCLC compared to non-tumor lung tissues of healthy individuals (from databases) and significantly associated with different clinicopathological features. It was also found that FTS, in a dose-dependent manner, suppressed proliferation of human A549 cells, while deltarasin reduced expression of HRAS in the lung cancer cells. To sum up, the results obtained from analyses based on bioinformatics databases indicate that the studied genes are potential risk factors for the development of lung cancer. On the other hand, studies of their expression on cell lines indicated that they may also be potentially important in the response to treatment using RAS inhibitors.

Keywords

• NSCLC
• <i>KRAS</i>
• <i>HRAS</i>
• RAS inhibitor
• farnesythiosalicylic acid
• deltarasin