REGγ is associated with multiple oncogenic pathways in human cancers

Background: Recent studies suggest a role of the proteasome activator, REG gamma, in cancer progression. Since there are limited numbers of known REG gamma targets, it is not known which cancers and pathways are associated with REG gamma. Methods: REG gamma protein expressions in four different cancers were investigated by immunohistochemistry (IHC) analysis. Following NCBI Gene Expression Omnibus (GEO) database search, microarray platform validation, differential expressions of REG gamma in corresponding cancers were statistically analyzed. Genes highly correlated with REG gamma were defined based on Pearson's correlation coefficient. Functional links were estimated by Ingenuity Core analysis. Finally, validation was performed by RT-PCR analysis in established cancer cell lines and IHC in human colon cancer tissues Results: Here, we demonstrate overexpression of REG gamma in four different cancer types by micro-tissue array analysis. Using meta-analysis of publicly available microarray databases and biological studies, we verified elevated REG gamma gene expression in the four types of cancers and identified genes significantly correlated with REG gamma expression, including genes in p53, Myc pathways, and multiple other cancer-related pathways. The predicted correlations were largely consistent with quantitative RT-PCR analysis. Conclusions: This study provides us novel insights in REG gamma gene expression profiles and its link to multiple cancer-related pathways in cancers. Our results indicate potentially important pathogenic roles of REG gamma in multiple cancer types and implicate REG gamma as a putative cancer marker.