TY - JOUR
T1 - Increased FOXJ1 protein expression is associated with improved overall survival in high-grade serous ovarian carcinoma
T2 - an Ovarian Tumor Tissue Analysis Consortium Study
AU - AOCS Group
AU - Weir, Ashley
AU - Kang, Eun Young
AU - Meagher, Nicola S.
AU - Nelson, Gregg S.
AU - Ghatage, Prafull
AU - Lee, Cheng Han
AU - Riggan, Marjorie J.
AU - Gentry-Maharaj, Aleksandra
AU - Ryan, Andy
AU - Singh, Naveena
AU - Widschwendter, Martin
AU - Alsop, Jennifer
AU - Anglesio, Michael S.
AU - Beckmann, Matthias W.
AU - Berger, Jessica
AU - Bisinotto, Christiani
AU - Boros, Jessica
AU - Brand, Alison H.
AU - Brenton, James D.
AU - Brooks-Wilson, Angela
AU - Carney, Michael E.
AU - Cunningham, Julie M.
AU - Cushing-Haugen, Kara L.
AU - Cybulski, Cezary
AU - Elishaev, Esther
AU - Erber, Ramona
AU - Fereday, Sian
AU - Fischer, Anna
AU - Paz-Ares, Luis
AU - Gayarre, Javier
AU - Gilks, Blake C.
AU - Grube, Marcel
AU - Harnett, Paul R.
AU - Harris, Holly R.
AU - Hartmann, Arndt
AU - Hein, Alexander
AU - Hendley, Joy
AU - Hernandez, Brenda Y.
AU - Heublein, Sabine
AU - Huang, Yajue
AU - Huzarski, Tomasz
AU - Jakubowska, Anna
AU - Jimenez-Linan, Mercedes
AU - Kennedy, Catherine J.
AU - Kommoss, Felix K.F.
AU - Koziak, Jennifer M.
AU - Kraemer, Bernhard
AU - Wang, Chen
AU - Winham, Stacey J.
AU - Goode, Ellen L.
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2023/1/26
Y1 - 2023/1/26
N2 - 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.
AB - 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.
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U2 - 10.1038/s41416-022-02014-y
DO - 10.1038/s41416-022-02014-y
M3 - Article
C2 - 36323878
AN - SCOPUS:85141178309
SN - 0007-0920
VL - 128
SP - 137
EP - 147
JO - British journal of cancer
JF - British journal of cancer
IS - 1
ER -