Low expression of prolyl hydroxylase 2 is associated with tumor grade and poor prognosis in patients with colorectal cancer

Previous studies have indicated that prolyl hydroxylases (PHDs) function as tumor suppressors in human colorectal cancer (CRC), but their clinical and prognostic significance is uncertain. Expressions of PHD1, PHD2, PHD3 and hypoxia-inducible factor (HIF)-1 alpha were detected using immunohistochemistry in an independent CRC cohort of 93 specimens represented on a tissue microarray (TMA). PHD expression levels were correlated with clinicopathological features, patient survival and presumed corresponding HIF-1 alpha expression. Pearson chi(2) test was used to compare clinicopathological features with protein expressions. Survival was estimated by Kaplan-Meier analysis. Cox regression analysis was performed for multivariate analysis of prognostic factors. Of the TMA, 47, 68 and 51 from 93 specimens had low expressions of PHD1, PHD2 and PHD3, respectively. HIF-1 alpha was positively expressed in 75 specimens. Low expression of PHD2 correlated with the highgrade group and a terrible overall survival (P = 0.017 and P = 0.032). Patients who had early stage CRC with low PHD2 expression had a poorer survival (P = 0.015), whereas patients with advanced-stage disease did not demonstrate such a difference (P = 0.691). Besides, PHD2 was uncorrelated with HIF-1 alpha expression. The present study indicated that low expression of PHD2 in CRC predicts poor survival independent of HIF-1 alpha, specifically for patients who have early stage tumors.