title: Expression of CDC6 and GDF-9 and their clinicopathological significances in benign and malignant lesions of the gallbladder.
abstract: OBJECTIVE
  Gallbladder cancers are cancers with high disease-specific mortality rates due to the lack of early diagnosis and effective therapy. In this study, we evaluated whether CDC6 and GDF-9 could be a marker for early diagnosis and target therapy.
  
  
  METHODS
  CDC6 and GDF-9 expressions in 108 gallbladder adenocarcinomas, 15 gallbladder polyps, 35 chronic cholecystitis tissues, and 46 peritumoral tissues were detected using immunohistochemistry (IHC).
  
  
  RESULTS
  We demonstrated that positive CDC6 and GDF-9 expressions were significantly higher in adenocarcinomas than that in peritumoral tissues, polyps, and chronic cholecystitis (p < 0.01). Benign lesions with positive CDC6 and negative GDF-9 expression showed moderately- or severely-atypical hyperplasia. The positive rates of CDC6 were significantly lower in cases with well-differentiated adenocarcinoma, small tumor mass, no metastasis of the lymph node, and no invasion of regional tissues (p < 0.05 or p < 0.01). In contrast, GDF-9 expression was significantly lower in the cases with poorly-differentiated adenocaarcinoma, lymph node metastasis, and invasion (p < 0.05 or p < 0.01). Univariate Kaplan-Meier analysis showed that CDC6 (p=0.046) or GDF-9 (p=0.032) expression was associated with decreased overall survival. Multivariate Cox regression analysis showed that increased expression of CDC6 (p=0.042) or decreased expression of GDF-9 (p=0.031) was an independent poor-prognostic predictor in gallbladder adenocarcinoma.
  
  
  CONCLUSIONS
  CDC6 and GDF-9 might be closely related to the carcinogenesis, clinical biological behaviors, and prognosis of gallbladder adenocarcinoma. The positive expression of CDC6 and negative expression of GDF-9 have poor-prognosis in gallbladder carcinoma.
authors.affiliation: Departemt of Geriatric Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Guo-Shun
authors.initials: GS
authors.lastname: Shu
authors.forename: Le-Ping
authors.initials: LP
authors.lastname: Yang
authors.forename: Zhu-Lin
authors.initials: ZL
authors.lastname: Yang
authors.forename: Song
authors.initials: S
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D055088:Early Detection of Cancer; D005260:Female; D005705:Gallbladder Diseases / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D005706:Gallbladder Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D055429:Growth Differentiation Factor 9 / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000096:biosynthesis*; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; C103706:CDC6 protein, human; D018797:Cell Cycle Proteins; D055429:Growth Differentiation Factor 9; D009687:Nuclear Proteins