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

被引：3

作者：

Weir, Ashley ^{[1
,2
,3
]}

Kang, Eun-Young ^{[4
]}

Meagher, Nicola S. ^{[1
,2
,5
]}

Nelson, Gregg S. ^{[6
]}

Ghatage, Prafull ^{[6
]}

Lee, Cheng-Han ^{[7
]}

Riggan, Marjorie J. ^{[8
]}

Gentry-Maharaj, Aleksandra ^{[9
]}

Ryan, Andy ^{[9
,10
]}

Singh, Naveena ^{[11
]}

Widschwendter, Martin ^{[12
]}

Alsop, Jennifer ^{[13
]}

Anglesio, Michael S. ^{[14
,15
,16
]}

Beckmann, Matthias W. ^{[17
]}

Berger, Jessica ^{[18
]}

Bisinotto, Christiani ^{[19
]}

Boros, Jessica ^{[20
,21
,22
]}

Brand, Alison H. ^{[21
,22
]}

Brenton, James D. ^{[23
]}

Brooks-Wilson, Angela ^{[24
]}

Carney, Michael E. ^{[25
]}

Cunningham, Julie M. ^{[26
]}

Cushing-Haugen, Kara L. ^{[27
]}

Cybulski, Cezary ^{[28
]}

Elishaev, Esther ^{[29
]}

Erber, Ramona ^{[30
]}

Fereday, Sian ^{[31
,32
]}

Fischer, Anna ^{[33
]}

Paz-Ares, Luis ^{[34
,35
]}

Gayarre, Javier ^{[36
]}

Gilks, Blake C. ^{[37
]}

Grube, Marcel ^{[38
]}

Harnett, Paul R. ^{[22
,39
]}

Harris, Holly R. ^{[27
,40
]}

Hartmann, Arndt ^{[30
]}

Hein, Alexander ^{[17
]}

Hendley, Joy ^{[31
]}

Hernandez, Brenda Y. ^{[41
]}

Heublein, Sabine ^{[42
]}

Huang, Yajue ^{[26
]}

Huzarski, Tomasz ^{[28
,43
]}

Jakubowska, Anna ^{[28
,44
]}

Jimenez-Linan, Mercedes ^{[45
]}

Kennedy, Catherine J. ^{[20
,21
,22
]}

Kommoss, Felix K. F. ^{[46
]}

Koziak, Jennifer M. ^{[47
]}

Kraemer, Bernhard ^{[38
]}

Le, Nhu D. ^{[48
]}

Lesnock, Jaime ^{[18
]}

Lester, Jenny ^{[49
]}

机构：

[1] Univ NSW Sydney, Sch Clin Med, UNSW Med & Hlth, Sydney, NSW, Australia

[2] Univ NSW Sydney, Lowy Canc Res Ctr, Adult Canc Program, Sydney, NSW, Australia

[3] Walter & Eliza Hall Inst Med Res, Parkville, Vic, Australia

[4] Univ Calgary, Foothills Med Ctr, Dept Pathol & Lab Med, Calgary, AB, Canada

[5] Univ Sydney, Daffodil Ctr, Sydney, NSW, Australia

[6] Univ Calgary, Cumming Sch Med, Dept Oncol, Div Gynecol Oncol, Calgary, AB, Canada

[7] Univ Alberta, Dept Pathol & Lab Med, Edmonton, AB, Canada

[8] Duke Univ Med Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, Durham, NC USA

[9] UCL, Inst Clin Trials & Methodol, MRC Clin Trials Unit, London, England

[10] UCL, Inst Womens Hlth, Womens Canc, London, England

[11] Barts Hlth Natl Hlth Serv Trust, Dept Pathol, London, England

[12] Univ Innsbruck, EUTOPS Inst, Innsbruck, Austria

[13] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge, England

[14] Univ British Columbia, Dept Obstet & Gynecol, Vancouver, BC, Canada

[15] Univ British Columbia, BC Canc, British Columbias Gynecol Canc Res Team OVCARE, Vancouver, BC, Canada

[16] Vancouver Gen Hosp, Vancouver, BC, Canada

[17] Friedrich Alexander Univ Erlangen Nuremberg, Univ Hosp Erlangen, Comprehens Canc Ctr Erlangen EMN, Dept Gynecol & Obstet, Erlangen, Germany

[18] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Div Gynecol Oncol, Pittsburgh, PA USA

[19] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Gynecol & Obstet, Ribeirao Preto, Brazil

[20] Univ Sydney, Ctr Canc Res, Westmead Inst Med Res, Sydney, NSW, Australia

[21] Westmead Hosp, Dept Gynaecol Oncol, Sydney, NSW, Australia

[22] Univ Sydney, Sydney, NSW, Australia

[23] Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge, England

[24] BC Canc, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC, Canada

[25] Univ Hawaii, John A Burns Sch Med, Dept Obstet & Gynecol, Honolulu, HI 96822 USA

[26] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA

[27] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, 1124 Columbia St, Seattle, WA 98104 USA

[28] Pomeranian Med Univ, Int Hereditary Canc Ctr, Dept Genet & Pathol, Szczecin, Poland

[29] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA

[30] Friedrich Alexander Univ Erlangen Nuremberg, Univ Hosp Erlangen, Comprehens Canc Ctr Erlangen EMN, Inst Pathol, Erlangen, Germany

[31] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia

[32] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic, Australia

[33] Tuebingen Univ Hosp, Inst Pathol & Neuropathol, Tubingen, Germany

[34] Spanish Natl Canc Res Ctr CNIO, H12O CNIO Lung Canc Clin Res Unit, Madrid, Spain

[35] Hosp Univ 12 Octubre, Oncol Dept, Madrid, Spain

[36] Spanish Natl Canc Res Ctr CNIO, Human Genet Grp, Madrid, Spain

[37] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC, Canada

[38] Tuebingen Univ Hosp, Dept Womens Hlth, Tubingen, Germany

[39] Westmead Hosp, Crown Princess Mary Canc Ctr, Sydney, NSW, Australia

[40] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA

[41] Univ Hawaii Canc Ctr, Honolulu, HI USA

[42] Univ Hosp Heidelberg, Dept Obstet & Gynecol, Heidelberg, Germany

[43] Univ Zielona Gora, Dept Genet & Pathol, Zielona Gora, Poland

[44] Pomeranian Med Univ, Independent Lab Mol Biol & Genet Diagnost, Szczecin, Poland

[45] Addenbrookes Hosp, Dept Histopathol, Cambridge, England

[46] Heidelberg Univ Hosp, Inst Pathol, Heidelberg, Germany

[47] Alberta Hlth Serv Canc Care, Calgary, AB, Canada

[48] BC Canc, Canc Control Res, Vancouver, BC, Canada

[49] Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA

[50] Pomeranian Med Univ, Dept Gynecol Surg & Gynecol Oncol Adults & Adoles, Szczecin, Poland

来源：

BRITISH JOURNAL OF CANCER | 2023年 / 128卷 / 01期

基金：

英国医学研究理事会; 加拿大健康研究院; 美国国家卫生研究院;

关键词：

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

D O I：

10.1038/s41416-022-02014-y

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

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.

引用

页码：137 / 147

页数：11

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