Use of a combination of approaches to identify and validate relevant tumor-associated antigens and their corresponding autoantibodies in ovarian cancer patients

被引:52
作者
Gagnon, Audrey [1 ]
Kim, Jae-Hoon [5 ]
Schorge, John O. [6 ]
Ye, Bin [4 ]
Liu, Brian [2 ]
Hasselblatt, Kathleen [1 ]
Welch, William R. [3 ]
Bandera, Christina A. [7 ]
Mok, Samuel C. [1 ]
机构
[1] Harvard Univ, Brigham & Womens Hosp, Sch Med,Div Gynecol Oncol, Dept Obstet Gynecol & Reprod Biol,Lab Gynecol Onc, Boston, MA 02115 USA
[2] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Urol, Boston, MA 02115 USA
[3] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA
[4] Harvard Univ, Brigham & Womens Hosp, Dept Obstet & Gynecol, Sch Med,Dana Farber Harvard Canc Ctr, Boston, MA 02115 USA
[5] Yonsei Univ, Coll Med, Dept Obstet & Gynecol, Yongdong Severance Hosp, Seoul, South Korea
[6] Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, Div Gynecol Oncol, Dallas, TX 75390 USA
[7] Brown Univ, Sch Med, Women & Infants Hosp, Program Womens Oncol, Providence, RI 02912 USA
关键词
D O I
10.1158/1078-0432.CCR-07-0856
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: 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. Experimental Design: 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.
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收藏
页码:764 / 771
页数:8
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