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Study On Ovarian Cancer Related Novel Antigen Genes

Posted on:2003-12-26Degree:DoctorType:Dissertation
Country:ChinaCandidate:J D WangFull Text:PDF
GTID:1104360185968682Subject:Oncology
Abstract/Summary:PDF Full Text Request
Objective: To evaluate the roles of novel antigen genes in diagnosis and immunothreapy of ovarian cancer and to analysis the relationship between novel antigen genes and the genesis of ovarian cancer.Methods: The genes selected by SEREX and SSH in our previously research works were identified after analysis by bioinformatics. 8 novel antigen phage clones were screened using allogenic sera from 98 patients with ovarian serous papillary cystadenoma. We detected the expression of OCY-66, OCY-189 and OCY-142 in 28 ovarian cancers and 30 normal ovarian tissues by RT-PCR, and studied the expression of OCY-142 in these ovarian cancers and normal ovarian tissues by nonradioactive hybridization in situ.Results: 55 positive clones were chosen randomly and sequenced. The sequencing results indicated that 55 positive clones represent 45 tumor antigen genes. 8 of them are novel genes, and they all have immunogenicity. OCY-142 is the novel-splicing variant of BARD1 (BRCA1 associated ring domain 1). It is located in chromosome 2 (2P13) and has one more intron sequences of BARD1 gene. It lost sequences coding for its RING domain and BRCT domain which are demonstrated responsible for interacting with the tumor suppressor gene BRCA1 and keeping its function. The immunogenicity of OCY-142 was also found derived from exposing of hide immuno-epitope by RING domain lost. OCY-142 may also be recognized by CD8~+T cell after MHC-I binding peptide prediction.The expression positive ratio of 8 novel antigen phage clones presented from 53.1%~91.8%, but with very low positive ratio in sera of 98 health donors. Using a combination of novel antigen genes, the sensitivity and specificity for detecting ovarian cancer is 96.9% and 95.2%, respectively. 36.9% of ovarian cancers with normal CA125 level can be detected out by OCY-142.
Keywords/Search Tags:Ovarian cancer, Tumor antigen, Tumor related gene, Tumor marker, Immunotherapy
PDF Full Text Request
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