Protocadherin γ-A7 is down-regulated in colorectal cancer and associated with the prognosis in patients with wild-type KRAS.

ABSTRACT

Many clustered protocadherin genes (PCDHs) within chromosome 5q31 are frequently down-regulated in colorectal cancer (CRC) due to the hypermethylation of this region, and some of them have been identified as tumor suppressors. However, the association between the expression of the clustered PCDHs and prognosis of CRC patients is still unclear. Here, we identified multiple PCDHs that were significantly down-regulated in CRC by analyzing the RNA-seq data of the Cancer Genome Atlas (TCGA) cohort. Among them, one γ-PCDH subfamily member, PCDHGA7, was found to be associated with overall survival in the patients with wild-type KRAS. Next, we experimentally validated the decrease of PCDHGA7 mRNA and protein levels in tumor tissues of 20 CRC patients by using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry assay (IHC). To further investigate whether the expression of PCDHGA7 could predict clinical outcomes, an independent cohort of 138 patients, whose tumors carried wild-type KRAS, was enrolled. In-house tissue microarrays (TMAs) were developed to facilitate the protein detection, and prognostic significance was analyzed. The result showed low PCDHGA7 expression was associated with advanced TNM stage, high risk of tumor recurrence and short overall survival. In conclusion, this study demonstrates that PCDHGA7 is down-regulated in CRC, and its expression level is correlated with clinical outcomes in patients with wild-type KRAS. Our finding indicates PCDHGA7 could serve as a potential novel biomarker to predict prognosis by combining certain tumor genotypes in patients of CRC.