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

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作   者：

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

作者机构：

John A Burns Sch Med;  Foothills Med Ctr;  Univ Sao Paulo;  Mayo Clin;  Div Epidemiol;  Rollins Sch Publ Hlth;  Struct Biol Programme;  Ctr Canc Res;  Familial Canc Unit;  Div Computat Biol;  Friedrich Alexander Univ Erlangen Nuremberg;  Univ NSW Sydney;  Hosp Univ 12 Octubre;  Ctr Canc Genet Epidemiol;  Sch Publ Hlth;  Emory Univ;  Med Univ South Carolina;  Univ Calgary;  Univ Hawaii;  Univ Alberta;  Univ Hawaii Canc Ctr;  University of New South Wales Sydney;  Dept Pathol & Lab Med;  Barts Hlth Natl Hlth Serv Trust;  Tuebingen Univ Hosp;  Univ Utah;  Int Hereditary Canc Ctr;  Addenbrookes Hosp;  Dept Gynecol Surg & Gynecol Oncol Adults & Adoles;  Ribeirao Preto Med Sch;  Inst Clin Trials & Methodol;  Canc Res UK Cambridge Inst;  Univ Sydney;  Alberta Hlth Serv Canc Care;  Peter MacCallum Canc Ctr;  Univ Hosp Erlangen;  Dept Pathol;  Cedars Sinai Canc;  H12O CNIO Lung Canc Clin Res Unit;  Div Clin Trials & Biostat;  Westmead Hosp;  Dept Obstet & Gynecol;  UCL;  Dept Lab Med & Pathol;  Univ Calif Los Angeles;  Canadas Michael Smith Genome Sci Ctr;  Dept Histopathol;  Human Genet Grp;  BC Canc;  Canc Control Res;  Huntsman Canc Inst;  Univ Cambridge;  Daffodil Ctr;  Univ Colorado;  EUTOPS Inst;  Dept Gynaecol Oncol;  Inst Pathol;  Univ Innsbruck;  Univ British Columbia;  Spanish Natl Canc Res Ctr CNIO;  Pomeranian Med Univ;  David Geffen Sch Med;  Cumming Sch Med;  Dept Womens Hlth;  Cedars Sinai Med Ctr;  Hollings Canc Ctr;  Duke Univ Med Ctr;  Tissue Pathol & Diagnost Oncol;  Sch Med;  Div Publ Hlth Sci;  Fred Hutchinson Canc Res Ctr;  Inst Pathol & Neuropathol;  Heidelberg Univ Hosp;  Univ Pittsburgh;  Univ Hosp Heidelberg; 

关键词：

INVASION;  PAX8 EXPRESSION;  GENE;  FALLOPIAN-TUBE;  CANCER;  MULTIPLE; 

期刊名称：

The British journal of cancer

i s s n：

0007-0920

年卷期：

2023 年 128 卷 1 期

页   码：

137-147

页   码：

摘   要：

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.