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oai:repisalud.isciii.es:20.500.12105/189002024-11-29T20:41:29Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud author Weir, Ashley author Kang, Eun-Young author Meagher, Nicola S author Nelson, Gregg S author Ghatage, Prafull author Lee, Cheng-Han author Riggan, Marjorie J author Gentry-Maharaj, Aleksandra author Ryan, Andy author Singh, Naveena author Widschwendter, Martin author Alsop, Jennifer author Anglesio, Michael S author Beckmann, Matthias W author Berger, Jessica author Bisinotto, Christiani author Boros, Jessica author Brand, Alison H author Brenton, James D author Brooks-Wilson, Angela author Carney, Michael E author Cunningham, Julie M author Cushing-Haugen, Kara L author Cybulski, Cezary author Elishaev, Esther author Erber, Ramona author Fereday, Sian author Fischer, Anna author Paz Ares, Luis Gonzaga author Gayarre, Javier author Gilks, Blake C author Grube, Marcel author Harnett, Paul R author Harris, Holly R author Hartmann, Arndt author Hein, Alexander author Hendley, Joy author Hernandez, Brenda Y author Heublein, Sabine author Huang, Yajue author Huzarski, Tomasz author Jakubowska, Anna author Jimenez-Linan, Mercedes author Kennedy, Catherine J author Kommoss, Felix K F author Koziak, Jennifer M author Kraemer, Bernhard author Le, Nhu D author Lesnock, Jaime author Lester, Jenny author Lubiński, Jan author Menkiszak, Janusz author Ney, Britta author Olawaiye, Alexander author Orsulic, Sandra author Osorio, Ana author Robles-Díaz, Luis author Ruebner, Matthias author Shah, Mitul author Sharma, Raghwa author Shvetsov, Yurii B author Steed, Helen author Talhouk, Aline author Taylor, Sarah E author Traficante, Nadia author Vierkant, Robert A author Wang, Chen author Wilkens, Lynne R author Winham, Stacey J author Benitez, Javier author Berchuck, Andrew author Bowtell, David D author Candido Dos Reis, Francisco J author Cook, Linda S author DeFazio, Anna author Doherty, Jennifer A author Fasching, Peter A author García, María J author Goode, Ellen L author Goodman, Marc T author Gronwald, Jacek author Huntsman, David G author Karlan, Beth Y author Kommoss, Stefan author Modugno, Francesmary author Schildkraut, Joellen M author Sinn, Hans-Peter author Staebler, Annette author Kelemen, Linda E author Ford, Caroline E author Menon, Usha author Pharoah, Paul D P author Köbel, Martin author Ramus, Susan J funder United States Department of Health and Human Services funder Canadian Institutes of Health Research funder National Health and Medical Research Council (Australia) funder Instituto de Salud Carlos III funder Ministerio de Ciencia, Innovación y Universidades (España) funder Ovarian Cancer Research Foundation (Astrualia) funder American Cancer Society funder Deutsche Forschungsgemeinschaft (Alemania) funder Unión Europea funder Cancer Council Victoria (Australia) funder Fred C. and Katherine B. Andersen Foundation funder Heuer Stiftung fur medizinische Forschung 2024-03-08T11:45:18Z 2024-03-08T11:45:18Z 2023-01 Br J Cancer . 2023;128(1):137-147 10.1038/s41416-022-02014-y 1532-1827 British journal of cancer 36323878 http://hdl.handle.net/20.500.12105/18900 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. eng Increased FOXJ1 protein expression is associated with improved overall survival in high-grade serous ovarian carcinoma: an Ovarian Tumor Tissue Analysis Consortium Study. journal article 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 URL https://repisalud.isciii.es/bitstreams/7b66d042-5084-4adc-a2ad-2e42cc0c18e0/download File MD5 c623e72b55fc8da00d5c55fe3739ddca 1331598 application/pdf increasedfoxj1proteinexpression_2022.pdf URL https://repisalud.isciii.es/bitstreams/41864594-54f1-45ac-ab60-e7ffc03a3734/download File MD5 aa73e13536152455944b61e71e9e6a9b 1905172 application/pdf 41416_2022_2014_MOESM1_ESM.pdf URL https://repisalud.isciii.es/bitstreams/3c471d45-0a1b-4495-9ae5-d73caa1dccd6/download File MD5 2cac123b0c7adad42ac6ab5986777a98 4804854 application/vnd.openxmlformats-officedocument.wordprocessingml.document 41416_2022_2014_MOESM2_ESM.docx URL https://repisalud.isciii.es/bitstreams/a63b91af-8138-40e6-9408-2f242c2796b9/download File MD5 b408f93692eda3e8dafb75ed3808a67f 124884 application/pdf 41416_2022_2014_MOESM3_ESM.pdf URL https://repisalud.isciii.es/bitstreams/f30e7d08-ae45-4257-8b19-b3f96d57602c/download File MD5 165b643b77b7ad1cf8e294d740c06591 174236 application/pdf 41416_2022_2014_MOESM4_ESM.pdf URL https://repisalud.isciii.es/bitstreams/d9344043-4cd2-4be8-a0f1-83423837effa/download File MD5 1963c3a0c7b7ebc2d8182298306b44dc 94940 application/pdf 41416_2022_2014_MOESM5_ESM.pdf URL https://repisalud.isciii.es/bitstreams/aeb8d246-e24d-4f06-9a45-7c95b07ca873/download File MD5 7db22ae775805d3b9f7629faa9c2588d 67835 text/plain increasedfoxj1proteinexpression_2022.pdf.txt URL https://repisalud.isciii.es/bitstreams/a665dd1a-ba5b-4ee1-b00d-e7d01a9f944a/download File MD5 6820fa3f01f719df824e43c4bd1081bd 5664 text/plain 41416_2022_2014_MOESM1_ESM.pdf.txt URL https://repisalud.isciii.es/bitstreams/5f6be328-29ed-46d9-88da-e0d0ec3f3174/download File MD5 917241c76bcb4ccc334bec311de62fcf 9165 text/plain 41416_2022_2014_MOESM3_ESM.pdf.txt URL https://repisalud.isciii.es/bitstreams/48ae967f-6ec0-4074-8726-3776a8a211c6/download File MD5 2288242f585a3a63268904a7adff8359 8284 text/plain 41416_2022_2014_MOESM4_ESM.pdf.txt URL https://repisalud.isciii.es/bitstreams/5e4de13b-bb5d-4d5f-b53b-eb87585ed75d/download File MD5 6a99c1b420246219f8815bb011f37bd7 6896 text/plain 41416_2022_2014_MOESM5_ESM.pdf.txt URL https://repisalud.isciii.es/bitstreams/01f6a5eb-7b5f-4a2c-ac53-e0e324926d70/download File MD5 665d3284b13748d33791e10a69adf257 11258 text/plain 41416_2022_2014_MOESM2_ESM.docx.txt