title: Use of a combination of approaches to identify and validate relevant tumor-associated antigens and their corresponding autoantibodies in ovarian cancer patients.
abstract: OBJECTIVE
  Novel biomarkers are urgently needed to increase the sensitivity of CA125 for the early detection of ovarian cancer. Indeed, it has been shown that as much as 20% of early-stage patients do not express significant levels of this biomarker. Therefore, the possibility of using autoantibodies directed against tumor-associated antigens as putative cancer markers is being more examined. Indeed, many autoantibodies have recently been shown to correlate with cancer patient prognosis or to be suitable for detection of the disease.
  
  
  METHODS
  In this study, we have used a new approach involving the use of proteomics, immunology, and ELISA methods to identify relevant autoantibodies in the plasma of ovarian cancer patients. To do so, we developed an innovative technique called two-dimensional differential gel electrophoresis analysis of immunoprecipitated tumor antigens.
  
  
  RESULTS
  This strategy allowed us to successfully identify novel circulating autoantibodies directed against the S100A7 protein in the plasma of ovarian cancer patients. Further real-time reverse transcription-PCR and immunohistochemical studies confirmed that the S100A7 mRNA and protein were highly expressed in ovarian tumors but absent in normal and benign tissues. Moreover, a preliminary study involving 138 patients confirmed that the plasma levels of anti-S100A7 antibodies are significantly elevated in early- and late-stage ovarian cancer patients compared with healthy controls and with patients with benign gynecologic diseases.
  
  
  CONCLUSIONS
  This shows that our approach is a valuable tool to successfully identify autoantibodies and tumor-associated antigens in cancer patients and that future research assessing their putative clinical usefulness would be worthwhile.
authors.affiliation: Laboratory of Gynecologic Oncology, Division of Gynecology Oncology, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Audrey
authors.initials: A
authors.lastname: Gagnon
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: John O
authors.initials: JO
authors.lastname: Schorge
authors.forename: Bin
authors.initials: B
authors.lastname: Ye
authors.forename: Brian
authors.initials: B
authors.lastname: Liu
authors.forename: Kathleen
authors.initials: K
authors.lastname: Hasselblatt
authors.forename: William R
authors.initials: WR
authors.lastname: Welch
authors.forename: Christina A
authors.initials: CA
authors.lastname: Bandera
authors.forename: Samuel C
authors.initials: SC
authors.lastname: Mok
mesh_terms: D000951:Antigens, Neoplasm / Q000097:blood* / Q000235:genetics / Q000276:immunology; D001323:Autoantibodies / Q000097:blood* / Q000235:genetics; D045744:Cell Line, Tumor; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D010051:Ovarian Neoplasms / Q000097:blood / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000951:Antigens, Neoplasm; D001323:Autoantibodies; D007074:Immunoglobulin G; D012333:RNA, Messenger; D012334:RNA, Neoplasm