title: Combined evaluation of centromere protein H and Ki-67 as prognostic biomarker for patients with gastric carcinoma.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gastrointestinal and Pancreatic Surgery and Centre of Gastric Cancer, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, PR China.
authors.forename: W L
authors.initials: WL
authors.lastname: He
authors.forename: Y H
authors.initials: YH
authors.lastname: Li
authors.forename: D J
authors.initials: DJ
authors.lastname: Yang
authors.forename: W
authors.initials: W
authors.lastname: Song
authors.forename: X L
authors.initials: XL
authors.lastname: Chen
authors.forename: F K
authors.initials: FK
authors.lastname: Liu
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.forename: W
authors.initials: W
authors.lastname: Chen
authors.forename: C Y
authors.initials: CY
authors.lastname: Chen
authors.forename: Y L
authors.initials: YL
authors.lastname: He
authors.forename: W H
authors.initials: WH
authors.lastname: Zhan
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D002277:Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D002503:Centromere / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D005163:Factor Analysis, Statistical; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D000077022:Survivin; D046888:Tissue Array Analysis; D015854:Up-Regulation
chemical_list: C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; C121933:CENPH protein, human; D002868:Chromosomal Proteins, Non-Histone; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000077022:Survivin