Abstract LB118: CEACAM7 as epigenetic prognostic marker in African Americans with lung adenocarcinoma
Authors: Tiv Richies , Jusue-Torres Ignacio , Mallisetty Apurva , Contreras-Vargas Leglys , Danilova Ludmila , Feldman Lawrence E. , Hulbert Alicia 
Published: June 2022

Background and Objectives of the Study: For the past several decades, lung cancer has had amongst the highest cancer incidence and mortality rates across the world. In the United States, African American (AA) individuals carry a disproportionate share of the lung cancer burden, with higher incidence, later-stage diagnosis, and poorer 5-year overall survival rate when compared with that of Whites. However, there is yet to be a race-specific biomarker for lung cancer. Most genomic data continue to include a small proportion of AA individuals, further contributing to the racial health disparity. Thus, the goal of our study was to conduct a genome-wide analysis to identify lung cancer biomarkers specific for AA individuals, to understand the role that these biomarkers play in overall survival, and to discover how epigenetic modulations may impact outcomes by race.

Methods: We utilized clinical and genomic data from The Cancer Genome Atlas (TCGA) for lung adenocarcinoma (LUAD). We conducted a differential expression analysis to identify the differentially expressed genes (DEGs) amongst AA individuals compared with Whites with LUAD. Two-tailed log rank tests with univariate and multivariate Cox proportional hazard models adjusted by age, gender, prior malignancy and stage were used to analyze overall survival for mRNA expression and DNA methylation for each racial subgroup. We investigated the epigenetic modifications that are correlated with the expression of the DEGs that play a significant role in the survival of AA individuals with lung cancer.

Results: CEACAM7 was the single gene that was both differentially expressed in AA individuals compared to Whites with LUAD and that had an impact on LUAD survival. CEACAM7 RNA expression showed trend towards significant direct correlation with LUAD stage in AA individuals but not for Whites. High RNA expression of CEACAM7 was associated with shorter median survival (P&lt;0.0001) and increased mortality risk HR: 11.84, 95% CI: 2.69-52.17 for AA individuals with LUAD, but there were no differences in survival time or risk for Whites. We also identified 5 CpG probes inversely correlated with the expression of CEACAM7 (cg22895231, cg25465322, cg01656853, cg17659920, and cg07940585). Each one of them showed that low methylation values had significantly shorter overall median survival. Only cg01656853 and cg07940585 showed association between lower DNA methylation levels and increased mortality risk in multivariate COX regression models.

Conclusion: This TCGA study suggests that the expression of CEACAM7 and its associated DNA methylation may play an important role in the survival of AA individuals with LUAD but not for Whites. Further studies are necessary to understand the mechanics of how the epigenetic regulation of CEACAM7 is associated with survival in AA individuals with LUAD and to identify new possible therapeutic targets.

Citation Format: Richies Tiv, Ignacio Jusue-Torres, Apurva Mallisetty, Leglys Contreras-Vargas, Ludmila Danilova, Lawrence E. Feldman, Alicia Hulbert. CEACAM7 as epigenetic prognostic marker in African Americans with lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB118.