Background: Lung cancer is the second most common cancer diagnosed in women. In fact, twice as many women will die from lung cancer compared to breast cancer, the key risk factor being tobacco use. Hence, there is a need to identify new molecular biomarkers to aid in early detection and develop new therapeutic strategies in tobacco-related lung cancer. Ras-like Estrogen-Regulated Growth-Inhibitory Gene (RERG) is a member of the Ras superfamily of GTPases that play an important role in cellular processes such as proliferation, differentiation, and apoptosis. Unlike other members of the Ras superfamily members of proto-oncogenes, RERG functions as a tumor suppressor.

Objective: To investigate the utility of RERG expression as a novel biomarker and a potential therapeutic target in lung cancer.

Results: In silico analysis of The Cancer Genome Atlas (TCGA) lung cancer datasets revealed a significant downregulation of RERG expression in lung tumors. Furthermore, reduced expression of RERG in lung tumors was also observed to be correlated with poor prognosis as determined by Kaplan-Meier survival analysis. Evaluation of formalin-fixed, paraffin-embedded (FFPE) human lung cancer tissues and fresh frozen lung tumor tissues corroborated our in silico observations. Most notably, tobacco smoke was identified to be associated with decreased RERG expression in lung tumors. The most intriguing observation from this study is the significant decrease of RERG expression in female smokers as a result of promoter hypermethylation.

Conclusion: Taken together, these findings suggest that RERG may represent a potential biomarker in lung cancer, particularly among smokers. Further investigation would focus on the mechanism of RERG loss and its influence on lung tumor development, particularly in female smokers.

Citation Format: Michelle Van Scoyk, Sreedevi Avasarala, Pei-Ying Wu, Yanlin Su, Lane Lerner, Alicia Hulbert, Kamesh Bikkavilli, Robert A. Winn. Ras-like estrogen-regulated growth-inhibitory gene (RERG): A novel biomarker and potential therapeutic target for women with lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5515.