Differential prognostic values of mRNA expression of CEACAM gene family members in nonsmall cell lung cancer

Serum carcinoembryonic antigen (CEA) is widely used as a representative marker of various malignant tumors. CEA-related cell adhesion molecules (CEACAMs), including CEACAM5, are encoded in the human genome by 12 independent genes and can be potential targets for future cancer treatments. In nonsmall cell lung cancer, serum CEA levels have been reported to predict patient survival. However, associations between mRNA expression of CEACAM gene family members in tumor tissues and patient prognosis remain unclear. To clarify this point, we used the Kaplan–Meier plotter global portal site, which collects the results of Affymetrix gene expression microarray analyses from the publicly accessible Gene Expression Omnibus database and combined it with survival data of patients. A total of 1,926 nonsmall cell lung cancer patients were identified from the Gene Expression Omnibus series, Cancer Biomedical Informatics Grid, and The Cancer Genome Atlas databases. We found statistically significant associations between mRNA expression of several CEACAMs and overall survival (OS) in patients with nonsmall cell lung cancer and lung adenocarcinoma (n=720) but not squamous cell carcinoma (n=524). In adenocarcinoma, higher expression levels of CEACAM6 and CEACAM8 were significantly associated with better OS, whereas higher expression levels of CEACAM3 , CEACAM4 , CEACAM19 , and CEACAM21 were associated with worse OS. Conflicting results among multiple probe sets for the same gene were found for CEACAM1 , CEACAM5 , and CEACAM7 . The findings of this study indicated that CEACAMs play important roles in tumor progression and impact OS of patients with adenocarcinoma. As the impact on OS differed based on the gene family members or the probe set used, the individual CEACAMs seem to function through complicated mechanisms. Further studies are necessary to resolve the problems encountered in our present study.