title: Overexpression of karyopherin 2 in human ovarian malignant germ cell tumor correlates with poor prognosis.
abstract: BACKGROUND
  The aim of this study was to identify a biomarker useful in the diagnosis and therapy of ovarian malignant germ cell tumor (OMGCT).
  
  
  METHODS
  The karyopherin 2 (KPNA2) expression in OMGCT and normal ovarian tissue was determined by standard gene microarray assays, and further validated by a quantitative RT-PCR and immunohistochemistry. The correlation between KPNA2 expression in OMGCT and certain clinicopathological features were analyzed. Expression of SALL4, a stem cell marker, was also examined in comparison with KPNA2.
  
  
  RESULTS
  KPNA2 was found to be over-expressed by approximately eight-fold in yolk sac tumors and immature teratomas compared to normal ovarian tissue by microarray assays. Overexpression was detected in yolk sac tumors, immature teratomas, dysgerminomas, embryonal carcinomas, mature teratomas with malignant transformation and mixed ovarian germ cell tumors at both the transcription and translation levels. A positive correlation between KPNA2 and SALL4 expression at both the transcription level (R = 0.5120, P = 0.0125), and the translation level (R = 0.6636, P<0.0001), was presented. Extensive expression of KPNA2 was positively associated with pathologic type, recurrence and uncontrolled, ascitic fluid presence, suboptimal cytoreductive surgery necessity, resistance/refraction to initial chemotherapy, HCG level and SALL4 level in OMGCT patients. KPNA2 was found to be an independent factor for 5-year disease-free survival (DFS) of OMGCT (P = 0.02). The 5-year overall survival (OS) and DFS rate for KPNA2-low expression patients (88% and 79%, n = 48) were significantly higher than the OS and DFS rate for KPNA2-high expression patients (69% and 57.1%, n = 42)(P = 0.0151, P = 0.0109, respectively). The 5-year OS and DFS rate for SALL4-low expression patients (84% and 74%, n = 62) was marginally significantly higher than the high expression patients (78.6% and 71.4%, n = 28)(P = 0.0519, P = 0.0647, respectively).
  
  
  CONCLUSIONS
  KPNA2 is a potential candidate molecular marker and important prognostic marker in OMGCT patients.
authors.affiliation: State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: He
authors.forename: Hui
authors.initials: H
authors.lastname: Ding
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Wang
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhou
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Yu
authors.forename: Long
authors.initials: L
authors.lastname: Huang
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Jia
authors.forename: Musheng
authors.initials: M
authors.lastname: Zeng
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Yun
authors.forename: Rong-Zhen
authors.initials: RZ
authors.lastname: Luo
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D005260:Female; D006801:Humans; D009373:Neoplasms, Germ Cell and Embryonal / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D010053:Ovary / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D014176:Protein Biosynthesis; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D015017:Yolk Sac / Q000378:metabolism* / Q000473:pathology; D028901:alpha Karyopherins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C490630:KPNA2 protein, human; C472575:SALL4 protein, human; D014157:Transcription Factors; D028901:alpha Karyopherins