LAUSR

Introduction: Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) result from the dual effects of smoking/pollution exposure and genetic susceptibility. Blacks/African Americans (B/AA) have higher tobacco-related morbidity and mortality than Whites/European Americans (W/EA), despite smoking fewer cigarettes and starting later in life. COPD is a well-established risk factor for LC and B/AA develop COPD with less cumulative smoking and at younger ages. We will test the hypothesis that NRF2 and Focal Adhesion-PI3K-Akt-mTOR-signaling pathways play a significant role in the disparities observed between B/AA and W/EA with LC and COPD and that account for worsened outcomes in B/AA. Methods: RNAseq analysis was conducted on tissues from 30 LC patients and 29 COPD patients undergoing lung transplantation. We compared both LC and COPD RNAseq data to identify common and unique transcripts associated with each disease. Results: A total of 153 genes were significantly upregulated in COPD compared to LC adeno carcinoma and 174 LC squamous cell carcinoma. Ingenuity pathway analysis revealed the involvement of top regulator networks with the activation of EPSA1, CTNNB1, EP300, IKBKB and IL1B which are seen in both LC and COPD and may be involved in COPD progression to LC. We further analyzed the transcriptome of COPD between B/AA and W/EA and identified 141 significantly upregulated genes in B/AAs. We further validated our findings in TCGA B/AA LC patients to determine the extent of overlap between COPD and LC. Among these, 42 (29.8%) and 13 (9.2%) genes were significantly upregulated in TCGA LC adenocarcinoma (58 B/AA patients vs 527 from other races) and LC squamous cell carcinoma cohorts (32 B/AA patients vs 518 from other races), respectively. Survival analysis using the upregulated genes from the TCGA LC B/AA cohorts showed a higher expression of three LC adenocarcinoma (TOMM5, CEP-152 and HGS) and two LC squamous cell carcinoma specific genes (PYROXD2 and USP43) significantly associated with overall survival. Conclusion: Our data provide novel insight on the overlap between COPD and LC and identified potential pathways that may be contributing to the significant health care disparity among B/AAs. Future studies are warranted to identify early-stage COPD markers that could be used for identification of high-risk individuals that would benefit from therapeutic interventions. Citation Format: Jose Thomas Thaiparambil, Zheng Yin, Randa El-Zein. Novel insights into lung cancer & chronic obstructive pulmonary disease racial disparities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1948.