title: Reduced expression of growth and differentiation factor-9 (GDF9) is associated with aggressive behaviour of human clear-cell renal cell carcinoma and poor patient survival.
abstract: BACKGROUND
  Growth and differentiation factor-9 (GDF9) is a member of the bone morphogentic protein (BMP) family. GDF9 was recently shown to be a regulator of the development and spread of cancer cells, including kidney cancer cells. However, the clinical implication of GDF9 in human clear-cell renal cell carcinoma (CCRCC) remains unknown. In the present study, the expression of GDF9 in human CCRCC tissues, and correlation between GDF9 and pathological grade and stage of the tumours were examined in CRCC specimens.
  
  
  METHODS
  The expression of GDF9 was examined in paired human normal renal and CCRCC tumour tissues (n=86). The expression of GDF9 in human renal tissues was assessed at both the mRNA and protein levels using reverse transcription-polymerase chain reaction and western blot. Furthermore, the survival curve was constructed using Kaplan-Meier method.
  
  
  RESULTS
  Decreased GDF9 protein levels were seen in CCRCC tissues compared with normal tissues. Low protein levels were seen in tumours with high clinical stages and with high pathological nuclear grade of CCRCC. Likewise, levels of GDF9 transcript in normal renal specimens was significantly higher than that in CCRCC tissues. The transcript levels of GDF9 differed significantly amongst different clinical stages and different pathological nuclear grade of CCRCC: The higher the clinical stage or pathological nuclear grade of CCRCC, the lower the transcript level of GDF9. Cumulative survival curves indicated that GDF9 mRNA expression was negatively correlated with cumulative survival time. Patients with high level of GDF9 had significantly longer survival time than the patients with low level of GDF9 (p<0.001).
  
  
  CONCLUSIONS
  GDF9 expression is markedly decreased in CCRCC, and is linked to pathological grade, clinical stage and long-term survival of the patients. This suggests that GDF9 is a potential tumour suppressor in CCRCC.
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Urology, Peking University Cancer Hospital & Institute, Beijing, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Du
authors.affiliation: Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Cardiff, U.K.
authors.forename: Lin
authors.initials: L
authors.lastname: Ye
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Urology, Peking University Cancer Hospital & Institute, Beijing, P.R. China yoya_urology@sina.com jiangw@cf.ac.uk.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Cardiff, U.K. yoya_urology@sina.com jiangw@cf.ac.uk.
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D055429:Growth Differentiation Factor 9 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C525897:GDF9 protein, human; D055429:Growth Differentiation Factor 9; D012333:RNA, Messenger
keywords: GDF9; Growth differentiation factor-9; cellular adhesion; clear-cell renal cell carcinoma; growth; invasion; migration