Combined evaluation of centromere protein H and Ki-67 as prognostic biomarker for patients with gastric carcinoma

摘要

Aim: Centromere protein H (CENP-H) is one of the essential components of the human active kinetochore which close links with carcinogenesis. Its expression and clinical value of prognostic prediction for gastric cancer (GC) is unclear. Methods: CENP-H and Ki-67 expressions in specimens from 166 patients with GC were determined by tissue microarrays and immunostaining. Their correlations between patients' clinicopathologic features and prognosis were explored. For mechanisms, quantitative CENP-H examination on gastric cancer tissue and cell lines was performed via real-time quantitative PCR and Western Blot. Its effect on Survivin expression and cell function was evaluated via CENP-H knocking down (SiRNA) or overexpression. Results: Highly expression of CENP-H was found in 85 of 166 GC, showing a significant correlation with tumour size, depth of infiltration, lymph node metastasis, distant metastasis and UICC staging of gastric carcinoma (P < 0.05), as well as clinical prognosis (coefficient = 0.550, P < 0.001). Multivariate analysis revealed that combined CENP-H and Ki67 expression was a more valuable independent prognostic predictor for patients' survival (hazard ratio, 2.18; P = 0.0109). Furthermore, total mRNA and protein expression of CENP-H in GC tissue and cell lines were noticeably increased. Survivin expression and cell function including growth, proliferation and clonogenic ability could be inhibited by CENP-H siRNA or enhanced by overexpressing CENP-H. Conclusion: High expression of CENP-H in GC indicates poor prognosis and Survivin may mediate its procancer role. Combined evaluation of CENP-H and Ki-67 aids in predicting the clinical prognosis.