ONCOmmunity

Increased FOXJ1 protein expression is associated with improved overall survival in high-grade serous ovarian carcinoma: an Ovarian Tumor Tissue Analysis Consortium Study.

By: Ashley Weir, Eun-Young Kang, Nicola S Meagher, Gregg S Nelson, Prafull Ghatage, Cheng-Han Lee, Marjorie J Riggan, Aleksandra Gentry-Maharaj, Andy Ryan, Naveena Singh, Martin Widschwendter, Jennifer Alsop, Michael S Anglesio, Matthias W Beckmann, Jessica Berger, Christiani Bisinotto, Jessica Boros, Alison H Brand, James D Brenton, Angela Brooks-Wilson, Michael E Carney, Julie M Cunningham, Kara L Cushing-Haugen, Cezary Cybulski, Esther Elishaev, Ramona Erber, Sian Fereday, Anna Fischer, Luis Paz-Ares, Javier Gayarre, Blake C Gilks, Marcel Grube, Paul R Harnett, Holly R Harris, Arndt Hartmann, Alexander Hein, Joy Hendley, Brenda Y Hernandez, Sabine Heublein, Yajue Huang, Tomasz Huzarski, Anna Jakubowska, Mercedes Jimenez-Linan, Catherine J Kennedy, Felix K F Kommoss, Jennifer M Koziak, Bernhard Kraemer, Nhu D Le, Jaime Lesnock, Jenny Lester, Jan Lubiński, Janusz Menkiszak, Britta Ney, Alexander Olawaiye, Sandra Orsulic, Ana Osorio, Luis Robles-Díaz, Matthias Ruebner, Mitul Shah, Raghwa Sharma, Yurii B Shvetsov, Helen Steed, Aline Talhouk, Sarah E Taylor, Nadia Traficante, Robert A Vierkant, Chen Wang, Lynne R Wilkens, Stacey J Winham, Javier Benitez, Andrew Berchuck, David D Bowtell, Francisco J Candido Dos Reis, Linda S Cook, Anna DeFazio, , Jennifer A Doherty, Peter A Fasching, María J García, Ellen L Goode, Marc T Goodman, Jacek Gronwald, David G Huntsman, Beth Y Karlan, Stefan Kommoss, Francesmary Modugno, Joellen M Schildkraut, Hans-Peter Sinn, Annette Staebler, Linda E Kelemen, Caroline E Ford, Usha Menon, Paul D P Pharoah, Martin Köbel, Susan J Ramus

School of Clinical Medicine, UNSW Medicine and Health, University of NSW Sydney, Sydney, NSW, Australia.
2022-1-25; doi: 10.1038/s41416-022-02014-y

Abstract

Background

Recently, we showed a >60% difference in 5-year survival for patients with tubo-ovarian high-grade serous carcinoma (HGSC) when stratified by a 101-gene mRNA expression prognostic signature. Given the varied patient outcomes, this study aimed to translate prognostic mRNA markers into protein expression assays by immunohistochemistry and validate their survival association in HGSC.

Methods

Two prognostic genes, FOXJ1 and GMNN, were selected based on high-quality antibodies, correlation with protein expression and variation in immunohistochemical scores in a preliminary cohort (n = 134 and n = 80, respectively). Six thousand four hundred and thirty-four (FOXJ1) and 5470 (GMNN) formalin-fixed, paraffin-embedded ovarian neoplasms (4634 and 4185 HGSC, respectively) represented on tissue microarrays from the Ovarian Tumor Tissue Analysis consortium underwent immunohistochemical staining and scoring, then univariate and multivariate survival analysis.

Results

Consistent with mRNA, FOXJ1 protein expression exhibited a linear, increasing association with improved overall survival in HGSC patients. Women with >50% expression had the most favourable outcomes (HR = 0.78, 95% CI 0.67-0.91, p < 0.0001). GMNN protein expression was not significantly associated with overall HSGC patient survival. However, HGSCs with >35% GMNN expression showed a trend for better outcomes, though this was not significant.

Conclusion

We provide foundational evidence for the prognostic value of FOXJ1 in HGSC, validating the prior mRNA-based prognostic association by immunohistochemistry.