AB055. Overexpression of CENPH is associated with tumor progression and prognosis of clear cell renal cell carcinoma

Objective: Centromere protein H (CENPH) is one of the essential components of the human active kinetochore which close links with carcinogenesis. Its biological and clinical value of prognostic prediction for human clear cell renal cell carcinoma (ccRCC) is unclear.

Methods: The expression levels of CENPH in ccRCC patients and cell lines were evaluated by quantitative real-time PCR (qRT-PCR) and Western blot. CENPH protein expressions in paraffin-embedded archival specimens from 107 patients with ccRCC were determined by immunohistochemical analysis. Their correlations between patients’ clinicopathologic features and prognosis were explored. Small-interfering RNA (siRNA) was used to suppress CENPH expression in RCC cell lines. In vitro assays were performed to further explore its role in tumor progression.

Results: The expression level of CENPH was higher in ccRCC tissues and cell lines than in corresponding adjacent normal tissues and normal human proximal tubule epithelial cell line HK-2. IHC analysis revealed high expression levels of CENPH in ccRCC specimens. The ccRCC patients with higher CENPH expression had an advanced clinical stage and poorer prognosis than those with lower CENPH expression. CENPH expression was an independent prognostic marker of overall RCC patient survival in a multivariate analysis. In vitro assays indicated that knockdown of CENPH reduced cell proliferation, apoptosis, and cell cycle arrest at G0/G1.

Conclusions: High expression of CENPH in ccRCC indicates poor prognosis. CENPH is a novel molecule involved in ccRCC progression, which provide a potential prognostic biomarker and therapeutic target.

Keywords: Clear cell renal cell carcinoma (ccRCC); centromere protein H (CENPH); proliferation; apoptosis