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CEACAM7 Expression and DNA Methylation: Prognostic Biomarkers for Lung Adenocarcinoma in African Americans
Alicia Hulbert1, Richies Tiv2, Brent Cao3
1Department of Surgery, University of Illinois at Chicago, College of Medicine, Chicago, Illinois; University of Illinois Hospital and Health Sciences System Cancer Center, University of Illinois at Chicago, Chicago, Illinois.
Introduction:
The goals of this study were to identify lung cancer biomarkers specific to African Americans (AA) by conducting a genome-wide analysis and to understand the role of these biomarkers in overall survival.
Material And Methods:
All cancers studied by The Cancer Genome Atlas were queried with the TCGAbiolinks R package (RRID:SCR_017683) for mRNA expression, DNA methylation, and clinical data. Differential expression analysis was performed comparing mRNA expression between AA and Whites. Survival duration differences were studied using the 2-tailed log-rank test. Association with survival was quantified using hazard ratios with 95% confidence intervals with univariate and multivariate Cox proportional hazard models. Spearman's rank correlation analysis was used to identify CpG sites correlated with mRNA expression.
Results:
CEACAM7 was the only gene overexpressed among AA compared with Whites with lung adenocarcinoma (LUAD), and its RNA expression was significantly associated with cancer stage, overall survival duration, and mortality risk in AA. DNA methylation on CpG probes cg22895231, cg25465322, cg01656853, cg17659920, and cg07940585 was negatively correlated with CEACAM7 mRNA expression, directly associated with survival duration, and inversely associated with mortality risk in AA with LUAD. Median survival was 37.29 months versus not reached for the high versus low CEACAM7 expression groups. The 1-, 2-, and 5-year survival rates for the high versus low CEACAM7 mRNA expression were 80% versus 100%, 50% versus 100%, and 20% versus 86%, respectively.
Conclusion:
CEACAM7 mRNA expression and its DNA methylation may be associated with overall survival duration and mortality risk among AA with LUAD but not in Whites.
