title: [Screening and sero-immunoscreening of ovarian epithelial cancer associative antigens].
abstract: OBJECTIVE
  To explore epithelial ovarian cancer (EOC) antigens that are potentially useful for cancer early detection and therapy.
  
  
  METHODS
  A high quality cDNA library derived from ascites tumor cells of EOC patients (3 cases of serous EOC, 1 case of mucinous EOC, and 1 case of endometrial carcinoma of ovary) was constructed, and the method of combining serological analysis of recombinant cDNA expression libraries (SEREX) and suppression subtractive hybridization (SSH) was used for screening cDNA library. All of the positive clones were sequenced and bioinformatics analysis with BLAST software in GenBank was performed. Serological mini-arrays of recombinant tumor antigens (SMARTA) was used to investigate the prevalence of autoantibodies to these antigens in both 96 ovarian cancer patients and 96 cancer-free controls.
  
  
  RESULTS
  Fifty-five positive clones encoding different antigenic genes of EOC recognized by IgG and (or) IgM were obtained. It showed that these 55 clones derived from 45 distinct genes and these genes could be grouped into 6 classes as following according to homology with known expressed sequence tag (EST): (1) known ovarian carcinoma related genes: BARD1, et al; (2) homologous genes with other tumors: TM4SF1, et al; (3) homologous genes with special tissues: ILF3, FXR1, et al; (4) homologous genes with special function: TIZ, C1D, et al; (5) embryo originating genes: PKHD1, et al; (6) novel genes: OV-189, et al. SMARTA results showed that the positive ratio of five EOC antigens TM4SF1 (28% vs. 9%), C1D (21% vs. 6%), BARD1 (23% vs. 5%), FXR1 (23% vs. 8%), OV-189 (31% vs. 13%) which reacting with their IgG autoantibodies, three antigens TIZ (26% vs. 8%), FXR1 (28% vs. 11%), and OV-189 (18% vs. 7%) which reacting with their IgM autoantibodies in patients was higher than in controls (P < 0.05). The positive ratio of EOC antigens FXR1 (34% vs. 16%), and OV-189 (46% vs. 23%) reacting with their IgG autoantibodies and TIZ (40% vs. 18%), FXR1 (46% vs. 18%) which reacting with their IgM autoantibodies in stage I-II patients was higher than that in stage III-IV (P < 0.05). The positive ratio of OV-189 (67% vs. 26%) which reacting with its IgG autoantibodies in well differentiated cases was higher than in moderately-poorly differentiated cases (P < 0.01). Combination of the above antigens showed a 66% sensitivity and 73% accuracy in discriminating EOC. Combination of the autoantibody profile of TM4SF1, C1D, TIZ, BARD1, FXR1, OV-189 with CA125 showed an 83% sensitivity and 80% accuracy in discriminating EOC.
  
  
  CONCLUSIONS
  The strategy of combination of SEREX and SSH is a potent tool in isolating tumor-associated antigen genes. Autoantibody profile of TM4SF1, C1D, TIZ, BARD1, FXR1, OV-189 are potential tumor markers in EOC detection.
authors.affiliation: Department of Gynecological Oncology, Tumor Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Zhi-jun
authors.initials: ZJ
authors.lastname: Yang
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Yan-ming
authors.initials: YM
authors.lastname: Jiang
authors.forename: Yu-liang
authors.initials: YL
authors.lastname: Ran
authors.forename: Zhi-hua
authors.initials: ZH
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Jie-qing
authors.initials: JQ
authors.lastname: Zhang
authors.forename: Zhong-mian
authors.initials: ZM
authors.lastname: Pan
authors.forename: Li
authors.initials: L
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000941:Antigens / Q000097:blood* / Q000235:genetics / Q000276:immunology; D000951:Antigens, Neoplasm / Q000097:blood* / Q000276:immunology; D014408:Biomarkers, Tumor / Q000276:immunology*; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D015723:Gene Library; D006801:Humans; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood / Q000276:immunology / Q000473:pathology; D010051:Ovarian Neoplasms / Q000097:blood / Q000276:immunology / Q000473:pathology; D055815:Young Adult
chemical_list: D000941:Antigens; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor