Autoantibody profiling to identify biomarkers of key pathogenic pathways in mucinous ovarian cancer

Tang, Liangdan; Yang, Junzheng; Ng, Shu-Kay; Rodriguez, Noah; Choi, Pui-Wah; Vitonis, Allison; Wang, Kui; McLachlan, Geoffrey J.; Caiazzo, Robert J.; Liu, Brian C.-S.; Welch, William R.; Cramer, Daniel W.; Berkowitz, Ross S.; Ng, Shu-Wing

doi:10.1016/j.ejca.2009.10.003

« Previous Next »European Journal of Cancer
Volume 46, Issue 1 , Pages 170-179, January 2010

Autoantibody profiling to identify biomarkers of key pathogenic pathways in mucinous ovarian cancer

Liangdan Tang
- Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Boston, MA 02115, USA
- Present address: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixue Yuan Road, Yuzhong District, Chongqing 400016, PR China.
Junzheng Yang
- Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Boston, MA 02115, USA
Shu-Kay Ng
- School of Medicine, Griffith University, Meadowbrook, QLD4131, Australia
Noah Rodriguez
- Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Boston, MA 02115, USA
Pui-Wah Choi
- Department of Biochemistry, Chinese University of Hong Kong, Hong Kong, China
Allison Vitonis
- Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Boston, MA 02115, USA
Kui Wang
- Department of Mathematics, University of Queensland, Brisbane, QLD4072, Australia
Geoffrey J. McLachlan
- Department of Mathematics, University of Queensland, Brisbane, QLD4072, Australia
Robert J. Caiazzo Jr.
- The Molecular Urology Laboratory, Division of Urology, Brigham and Women’s Hospital, Boston, MA 02115, USA
Brian C.-S. Liu
- The Molecular Urology Laboratory, Division of Urology, Brigham and Women’s Hospital, Boston, MA 02115, USA
William R. Welch
- Department of Pathology, Brigham and Women’s Hospital, Boston, MA 02115, USA
Daniel W. Cramer
- Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Boston, MA 02115, USA
Ross S. Berkowitz
- Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Boston, MA 02115, USA
Shu-Wing Ng
- Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Boston, MA 02115, USA
- Corresponding author: Address: Laboratory of Gynecologic Oncology, 221 Longwood Avenue, Brigham and Women’s Hospital, Boston, MA 02115, USA. Tel.: +1 617 278 0072; fax: +1 617 975 0856.

Received 11 September 2009; accepted 1 October 2009. published online 18 November 2009.

Abstract

Mucinous epithelial ovarian cancers are clinically and morphologically distinct from the other histopathologic subtypes of ovarian cancer. Unlike other ovarian subtypes, epidemiologic studies have indicated that tobacco exposure is a significant risk factor for developing mucinous ovarian cancer. Detection of autoantibody reactivity is useful in biomarker discovery and for explaining the role of important pathophysiologic pathways in disease. In order to study if there are specific antibody biomarkers in the plasma samples of mucinous ovarian cancer patients, we have initiated a screen by employing a ‘reverse capture antibody microarray’ platform that uses native host antigens derived from mucinous ovarian tissues as ‘baits’ for the capture of differentially labelled patient and control autoantibodies. Thirty-five autoantibodies that were significantly elevated in the cancer plasma samples compared with healthy controls, and six autoantibodies that segregated smoking and non-smoking patients were identified. Functional annotation of the antibody targets has identified nine target antigens involved in integrin and Wnt signalling pathways. Immunohistochemistry of archived ovarian specimens showed significant overexpression of eight of the nine target antigens in mucinous ovarian tumour tissues, suggesting that plasma autoantibodies from mucinous ovarian cancer patients might have heightened reactivities with epitopes presented by these overexpressed antigens. Autoantibody profiling may have an unexpected utility in uncovering key signalling pathways that are dysregulated in the system of interest.

Keywords: Autoantibody, Ovarian cancer, Smoking, Profiling, Signalling pathway