title: [Analysis of differentially expressed proteins in normal cervix, cervical intraepithelial neoplasia and cervical squamous carcinoma tissues].
abstract: OBJECTIVE
  To explore the differentially expressed proteins in normal cervix, cervical intraepithelial neoplasia (CIN) and squamous cervical carcinoma (SCC) tissues by differential proteomics, and to provide a basis for studies on CIN molecular pathogenesis, clinical diagnosis and treatment.
  
  
  METHODS
  Uterine cervical tissue specimens from the patients treated between August 2008 and September 2009 in the Department of Oncology of Beijing Obstetrics and Gynecology Hospital were collected. There were samples of normal cervix (n = 9), CIN (n = 23, CIN I = 7, CIN II = 8, CIN III = 8) and SCC (n = 7). 2-D DIGE and DeCyder software were used to detect the differentially expressed protein-spots. Then MALDI-TOF/TOF MS was used to analyze the differentially expressed proteins. Collect normal cervix(n = 20), CIN (n = 60) and SCC (n = 20), immunohistochemistry (IHC) and Western blot were used to verify the differentially expressed proteins of S100A9 (S100 calcium-binding protein A9) , eEF1A1 (eukaryotic elongation factor 1-alpha-1) and PKM2 (pyruvate kinase isozymes M2) among the normal cervix, CIN and SCC tissues. Immunohistochemistry was used to detect the differentially expressed S100A9, eEF1A1 and PKM2 in the cervical tissues.
  
  
  RESULTS
  2D gel electrophoresis images with high resolution and good repeatability were obtained. Forty-six differentially expressed proteins (27 were up-regulated and 19 were down-regulated) were selected among the normal, CIN, and SCC, and 26 proteins were successfully identified. Immunohistochemistry showed that protein S100A9 was mainly expressed in the cytoplasm, and its positive expression rate was 20.0% in normal cervical mucosa, 70.0% in CIN, and 100.0% in squamous cell carcinoma, with a significant difference between them (P = 0.006). eEF1A1 was mainly expressed in the cell plasma. Its positive expression rate was 70.0% in normal cervix, 73.3%in CIN and 60.0% in SCC tissues, with a non-significant difference between them (P = 0.758). The protein PKM2 was mainly expressed in the cell nuclei. Its positive expression rate was 100.0% in normal cervix, 93.3% in CIN and 75.0% in SCC tissues, showing a difference close to statistical significance (P = 0.059) between them. The results of Western blot were similar with that of immunohistochemical examination.
  
  
  CONCLUSIONS
  There are differentially expressed proteins among normal cervix, CIN and SCC. S100A9, eEF1A1 and PKM2 may become candidate markers for early diagnosis of cervical cancer and new targets for therapy. It also provides a further basis for studies of the pathogenetic mechanism of CIN developing to cervical cancer.
authors: Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100006, China.
authors: Qun
authors: Q
authors: Zhao
authors: Email: wym597118@163.com.
authors: Yu-mei
authors: YM
authors: Wu
authors: Yue
authors: Y
authors: He
authors: Xiao-li
authors: XL
authors: Wang
authors: Shuo
authors: S
authors: Chen
authors: Xiao-hong
authors: XH
authors: Qian
authors: Yu-xiang
authors: YX
authors: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D040502:Calgranulin B / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002584:Cervix Uteri / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D020648:Peptide Elongation Factor 1 / Q000378:metabolism; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013963:Thyroid Hormones / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism*; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000378:metabolism*; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D014408:Biomarkers, Tumor; D040502:Calgranulin B; D002352:Carrier Proteins; D008565:Membrane Proteins; D020648:Peptide Elongation Factor 1; D013963:Thyroid Hormones; D000097810:Thyroid Hormone-Binding Proteins; C094814:EEF1A1 protein, human