AB245. Down-regulation of C12orf59 is associated with a poor prognosis and VHL mutations in renal cell carcinoma

BACKGROUND: The aim of this study was to investigate the expression and prognostic value of C12orf59 in ccRCC. METHODS: In silico gene expression was performed to analyze C12orf59 mRNA expression. The mRNA and protein expression levels of C12orf59 were assessed by real-time PCR and western blotting in a panel of cancer cell lines and 40 paired primary RCC and corresponding adjacent noncancerous tissues. Immunohistochemistry on additional renal tumor tissues was performed to study the C12orf59 expression and its association with clinico-pathological parameters (n=204), disease outcomes, the VHL gene, the UMPP gene and chromatin remodeling gene mutations (n=86), and HIF1α and HIF2α protein levels (n=86). RESULTS: C12orf59 mRNA was broadly expressed in normal human tissues with high expression levels in the kidney, and the C12orf59 protein was located in the cytoplasm. A panel of cancer cell lines lacked detectable C12orf59 expression, and C12orf59 expression was significantly down-regulated in renal cell carcinoma (RCC) compared with corresponding adjacent noncancerous tissues (P<0.01). The loss of C12orf59 was correlated with lymph node status (P<0.05), distant metastases (P<0.05), poor survival (P<0.001) (HR 3.00; 95% CI, 1.29–7.53), VHL non-sense mutations or frame-shift mutations (P<0.01), and UMPP gene non-sense mutations or frame-shift mutations (P=0.01). CONCLUSIONS: C12orf59 expression was significantly down-regulated in RCC, and C12orf59 may serve as a prognostic biomarker of ccRCC with potential applications as a target for future functional studies. Decreased C12orf59 expression is associated with the loss of VHL and may cooperate with the loss of VHL to promote renal carcinogenesis.