PURPOSE: A better understanding of the molecular pathways underlying the development of epithelial ovarian cancer (EOC) is critical to identify ovarian tumor markers for use in diagnostic or therapeutic applications. The aims of this study were to integrate the results from 14 transcript profiling studies of EOC to identify novel biomarkers and to examine their expression in early and late stages of the disease. EXPERIMENTAL DESIGN: A database incorporating genes identified as being highly up-regulated in each study was constructed. Candidate tumor markers were selected from genes that overlapped between studies and by evidence of surface membrane or secreted expression. The expression patterns of three integral membrane proteins, discoidin domain receptor 1 (DDR1), claudin 3 (CLDN3), and epithelial cell adhesion molecule, all of which are involved in cell adhesion, were evaluated in a cohort of 158 primary EOC using immunohistochemistry. RESULTS: We confirmed that these genes are highly overexpressed in all histological subtypes of EOC compared with normal ovarian surface epithelium, identifying DDR1 and CLDN3 as new biomarkers of EOC. Furthermore, we determined that these genes are also expressed in ovarian epithelial inclusion cysts, a site of metaplastic changes within the normal ovary, in borderline tumors and in low-grade and stage cancer. A trend toward an association between low CLDN3 expression and poor patient outcome was also observed. CONCLUSIONS: These results suggest that up-regulation of DDR1, CLDN3, and epithelial cell adhesion molecule are early events in the development of EOC and have potential application in the early detection of disease.
PURPOSE: A better understanding of the molecular pathways underlying the development of epithelial ovarian cancer (EOC) is critical to identify ovarian tumor markers for use in diagnostic or therapeutic applications. The aims of this study were to integrate the results from 14 transcript profiling studies of EOC to identify novel biomarkers and to examine their expression in early and late stages of the disease. EXPERIMENTAL DESIGN: A database incorporating genes identified as being highly up-regulated in each study was constructed. Candidate tumor markers were selected from genes that overlapped between studies and by evidence of surface membrane or secreted expression. The expression patterns of three integral membrane proteins, discoidin domain receptor 1 (DDR1), claudin 3 (CLDN3), and epithelial cell adhesion molecule, all of which are involved in cell adhesion, were evaluated in a cohort of 158 primary EOC using immunohistochemistry. RESULTS: We confirmed that these genes are highly overexpressed in all histological subtypes of EOC compared with normal ovarian surface epithelium, identifying DDR1 and CLDN3 as new biomarkers of EOC. Furthermore, we determined that these genes are also expressed in ovarian epithelial inclusion cysts, a site of metaplastic changes within the normal ovary, in borderline tumors and in low-grade and stage cancer. A trend toward an association between low CLDN3 expression and poor patient outcome was also observed. CONCLUSIONS: These results suggest that up-regulation of DDR1, CLDN3, and epithelial cell adhesion molecule are early events in the development of EOC and have potential application in the early detection of disease.
Authors: Paul P Szotek; Henry L Chang; Kristen Brennand; Akihiro Fujino; Rafael Pieretti-Vanmarcke; Cristina Lo Celso; David Dombkowski; Frederic Preffer; Kenneth S Cohen; Jose Teixeira; Patricia K Donahoe Journal: Proc Natl Acad Sci U S A Date: 2008-08-18 Impact factor: 11.205
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Authors: Narasimhan Kothandaraman; Vladimir B Bajic; Pang N K Brendan; Chan Y Huak; Peh B Keow; Khalil Razvi; Manuel Salto-Tellez; Mahesh Choolani Journal: BMC Cancer Date: 2010-02-24 Impact factor: 4.430
Authors: Jennifer A Byrne; Sanaz Maleki; Jayne R Hardy; Brian S Gloss; Rajmohan Murali; James P Scurry; Susan Fanayan; Catherine Emmanuel; Neville F Hacker; Robert L Sutherland; Anna Defazio; Philippa M O'Brien Journal: BMC Cancer Date: 2010-09-17 Impact factor: 4.430
Authors: Jose I Martin-Subero; Ole Ammerpohl; Marina Bibikova; Eliza Wickham-Garcia; Xabier Agirre; Sara Alvarez; Monika Brüggemann; Stefanie Bug; Maria J Calasanz; Martina Deckert; Martin Dreyling; Ming Q Du; Jan Dürig; Martin J S Dyer; Jian-Bing Fan; Stefan Gesk; Martin-Leo Hansmann; Lana Harder; Sylvia Hartmann; Wolfram Klapper; Ralf Küppers; Manuel Montesinos-Rongen; Inga Nagel; Christiane Pott; Julia Richter; José Román-Gómez; Marc Seifert; Harald Stein; Javier Suela; Lorenz Trümper; Inga Vater; Felipe Prosper; Claudia Haferlach; Juan Cruz Cigudosa; Reiner Siebert Journal: PLoS One Date: 2009-09-11 Impact factor: 3.240
Authors: Jianghong Li; Cheryl A Sherman-Baust; Miyun Tsai-Turton; Robert E Bristow; Richard B Roden; Patrice J Morin Journal: BMC Cancer Date: 2009-07-20 Impact factor: 4.430
Authors: C A Barton; B S Gloss; W Qu; A L Statham; N F Hacker; R L Sutherland; S J Clark; P M O'Brien Journal: Br J Cancer Date: 2009-11-24 Impact factor: 7.640