Abstract Although glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is often considered to be a stable housekeeping marker gene, we recently determined that high levels of GAPDH mRNA expression in solid tumors was highly correlated with the expression of a group of genes, most of which are classified as cell cycle-dependent (Wang et al. PLoS One, 2013). In the current project, we have further evaluated the role of GAPDH in lung adenocarcinoma. Using data from an integrated microarray gene expression dataset and The Cancer Genome Atlas (TCGA) Project, we have now found a correlation between high mRNA expression of GAPDH and low expression of the tumor suppressor gene Deleted in Liver Cancer-1 (DLC1). DLC1 encodes a protein with strong RhoGAP (GTPase activating protein) activity and is inactivated in various human malignancies. In lung adenocarcinoma, low DLC1 expression occurred frequently together with up-regulation of GAPDH. The correlation coefficient of GAPDH and DLC1 expression in the integrated gene expression dataset was -0.6. In addition, high GAPDH and low DLC1 expression in lung cancer was associated with unfavorable prognosis. The combination of DLC1 expression level and GAPDH level improved the predictive prognostic power compared with that of the individual gene level alone. Pathway analysis indicated that low DLC1 in lung cancer was accompanied by increased expression of genes implicated in glycolysis and reduced expression of fructose-1,6-bisphosphatase (FBP1) in gluconeogenesis. Our findings suggest that GAPDH may contribute to the regulation of cell cycle genes and of tumor suppressor genes in cancer. Citation Format: Dunrui Wang, Guangxian Zhang. High expression of GAPDH is relevant to lung adenocarcinoma with low expression of the tumor suppressor gene Deleted in Liver Cancer-1 (DLC1). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2367. doi:10.1158/1538-7445.AM2014-2367