Prognostic gene expression signature for high-grade serous ovarian cancer

J. Millstein; T. Budden; E. L. Goode; M. S. Anglesio; A. Talhouk; M. P. Intermaggio; H. S. Leong; S. Chen; W. Elatre; B. Gilks; T. Nazeran; M. Volchek; R. C. Bentley; C. Wang; D. S. Chiu; S. Kommoss; S. C. Y. Leung; J. Senz; A. Lum; V. Chow; H. Sudderuddin; R. Mackenzie; J. George; S. Fereday; J. Hendley; N. Traficante; H. Steed; J. M. Koziak; M. Köbel; I. A. McNeish; T. Goranova; D. Ennis; G. Macintyre; D. Silva De Silva; T. Ramón y Cajal; J. García-Donas; S. Hernando Polo; G. C. Rodriguez; K. L. Cushing-Haugen; H. R. Harris; C. S. Greene; R. A. Zelaya; S. Behrens; R. T. Fortner; P. Sinn; E. Herpel; J. Lester; J. Lubiński; O. Oszurek; A. Tołoczko; C. Cybulski; J. Menkiszak; C. L. Pearce; M. C. Pike; C. Tseng; J. Alsop; V. Rhenius; H. Song; M. Jimenez-Linan; A. M. Piskorz; A. Gentry-Maharaj; C. Karpinskyj; M. Widschwendter; N. Singh; C. J. Kennedy; R. Sharma; et al.

doi:10.1016/j.annonc.2020.05.019

Prognostic gene expression signature for high-grade serous ovarian cancer

J. Millstein
, T. Budden
, E. L. Goode
, M. S. Anglesio
, A. Talhouk
, M. P. Intermaggio
, H. S. Leong
, S. Chen
, W. Elatre
, B. Gilks
, T. Nazeran
, M. Volchek
, R. C. Bentley
, C. Wang
, D. S. Chiu
, S. Kommoss
, S. C. Y. Leung
, J. Senz
, A. Lum
, V. Chow

H. Sudderuddin, R. Mackenzie, J. George, S. Fereday, J. Hendley, N. Traficante, H. Steed, J. M. Koziak, M. Köbel, I. A. McNeish, T. Goranova, D. Ennis, G. Macintyre, D. Silva De Silva, T. Ramón y Cajal, J. García-Donas, S. Hernando Polo, G. C. Rodriguez, K. L. Cushing-Haugen, H. R. Harris, C. S. Greene, R. A. Zelaya, S. Behrens, R. T. Fortner, P. Sinn, E. Herpel, J. Lester, J. Lubiński, O. Oszurek, A. Tołoczko, C. Cybulski, J. Menkiszak, C. L. Pearce, M. C. Pike, C. Tseng, J. Alsop, V. Rhenius, H. Song, M. Jimenez-Linan, A. M. Piskorz, A. Gentry-Maharaj, C. Karpinskyj, M. Widschwendter, N. Singh, C. J. Kennedy, R. Sharma, et al.

Western Sydney University

Research output: Contribution to journal › Article › peer-review

107 Citations (Scopus)

Abstract

Background: Median overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is ∼4 years, yet survival varies widely between patients. There are no well-established, gene expression signatures associated with prognosis. The aim of this study was to develop a robust prognostic signature for OS in patients with HGSOC. Patients and methods: Expression of 513 genes, selected from a meta-analysis of 1455 tumours and other candidates, was measured using NanoString technology from formalin-fixed paraffin-embedded tumour tissue collected from 3769 women with HGSOC from multiple studies. Elastic net regularization for survival analysis was applied to develop a prognostic model for 5-year OS, trained on 2702 tumours from 15 studies and evaluated on an independent set of 1067 tumours from six studies. Results: Expression levels of 276 genes were associated with OS (false discovery rate < 0.05) in covariate-adjusted single-gene analyses. The top five genes were TAP1, ZFHX4, CXCL9, FBN1 and PTGER3 (P < 0.001). The best performing prognostic signature included 101 genes enriched in pathways with treatment implications. Each gain of one standard deviation in the gene expression score conferred a greater than twofold increase in risk of death [hazard ratio (HR) 2.35, 95% confidence interval (CI) 2.02–2.71; P < 0.001]. Median survival [HR (95% CI)] by gene expression score quintile was 9.5 (8.3 to –), 5.4 (4.6–7.0), 3.8 (3.3–4.6), 3.2 (2.9–3.7) and 2.3 (2.1–2.6) years. Conclusion: The OTTA-SPOT (Ovarian Tumor Tissue Analysis consortium - Stratified Prognosis of Ovarian Tumours) gene expression signature may improve risk stratification in clinical trials by identifying patients who are least likely to achieve 5-year survival. The identified novel genes associated with the outcome may also yield opportunities for the development of targeted therapeutic approaches.

Original language	English
Pages (from-to)	1240-1250
Number of pages	11
Journal	Annals of Oncology
Volume	31
Issue number	9
DOIs	https://doi.org/10.1016/j.annonc.2020.05.019
Publication status	Published - 1 Sept 2020

Bibliographical note

Publisher Copyright:
© 2020 The Authors

Open Access - Access Right Statement

© 2020 The Authors. Published by Elsevier Ltd on behalf of European Society for Medical Oncology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

cancer
gene expression
ovaries
prognosis

Access to Document

10.1016/j.annonc.2020.05.019

Cite this

Millstein, J., Budden, T., Goode, E. L., Anglesio, M. S., Talhouk, A., Intermaggio, M. P., Leong, H. S., Chen, S., Elatre, W., Gilks, B., Nazeran, T., Volchek, M., Bentley, R. C., Wang, C., Chiu, D. S., Kommoss, S., Leung, S. C. Y., Senz, J., Lum, A., ... et al. (2020). Prognostic gene expression signature for high-grade serous ovarian cancer. Annals of Oncology, 31(9), 1240-1250. https://doi.org/10.1016/j.annonc.2020.05.019

@article{8a5addc0e97a474896c94bfa6860fad5,

title = "Prognostic gene expression signature for high-grade serous ovarian cancer",

abstract = "Background: Median overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is ∼4 years, yet survival varies widely between patients. There are no well-established, gene expression signatures associated with prognosis. The aim of this study was to develop a robust prognostic signature for OS in patients with HGSOC. Patients and methods: Expression of 513 genes, selected from a meta-analysis of 1455 tumours and other candidates, was measured using NanoString technology from formalin-fixed paraffin-embedded tumour tissue collected from 3769 women with HGSOC from multiple studies. Elastic net regularization for survival analysis was applied to develop a prognostic model for 5-year OS, trained on 2702 tumours from 15 studies and evaluated on an independent set of 1067 tumours from six studies. Results: Expression levels of 276 genes were associated with OS (false discovery rate < 0.05) in covariate-adjusted single-gene analyses. The top five genes were TAP1, ZFHX4, CXCL9, FBN1 and PTGER3 (P < 0.001). The best performing prognostic signature included 101 genes enriched in pathways with treatment implications. Each gain of one standard deviation in the gene expression score conferred a greater than twofold increase in risk of death [hazard ratio (HR) 2.35, 95\% confidence interval (CI) 2.02–2.71; P < 0.001]. Median survival [HR (95\% CI)] by gene expression score quintile was 9.5 (8.3 to –), 5.4 (4.6–7.0), 3.8 (3.3–4.6), 3.2 (2.9–3.7) and 2.3 (2.1–2.6) years. Conclusion: The OTTA-SPOT (Ovarian Tumor Tissue Analysis consortium - Stratified Prognosis of Ovarian Tumours) gene expression signature may improve risk stratification in clinical trials by identifying patients who are least likely to achieve 5-year survival. The identified novel genes associated with the outcome may also yield opportunities for the development of targeted therapeutic approaches.",

keywords = "cancer, gene expression, ovaries, prognosis",

author = "J. Millstein and T. Budden and Goode, \{E. L.\} and Anglesio, \{M. S.\} and A. Talhouk and Intermaggio, \{M. P.\} and Leong, \{H. S.\} and S. Chen and W. Elatre and B. Gilks and T. Nazeran and M. Volchek and Bentley, \{R. C.\} and C. Wang and Chiu, \{D. S.\} and S. Kommoss and Leung, \{S. C. Y.\} and J. Senz and A. Lum and V. Chow and H. Sudderuddin and R. Mackenzie and J. George and S. Fereday and J. Hendley and N. Traficante and H. Steed and Koziak, \{J. M.\} and M. K{\"o}bel and McNeish, \{I. A.\} and T. Goranova and D. Ennis and G. Macintyre and \{Silva De Silva\}, D. and \{Ram{\'o}n y Cajal\}, T. and J. Garc{\'i}a-Donas and \{Hernando Polo\}, S. and Rodriguez, \{G. C.\} and Cushing-Haugen, \{K. L.\} and Harris, \{H. R.\} and Greene, \{C. S.\} and Zelaya, \{R. A.\} and S. Behrens and Fortner, \{R. T.\} and P. Sinn and E. Herpel and J. Lester and J. Lubi{\'n}ski and O. Oszurek and A. To{\l}oczko and C. Cybulski and J. Menkiszak and Pearce, \{C. L.\} and Pike, \{M. C.\} and C. Tseng and J. Alsop and V. Rhenius and H. Song and M. Jimenez-Linan and Piskorz, \{A. M.\} and A. Gentry-Maharaj and C. Karpinskyj and M. Widschwendter and N. Singh and Kennedy, \{C. J.\} and R. Sharma and \{et al.\}",

note = "Publisher Copyright: {\textcopyright} 2020 The Authors",

year = "2020",

month = sep,

day = "1",

doi = "10.1016/j.annonc.2020.05.019",

language = "English",

volume = "31",

pages = "1240--1250",

journal = "Annals of Oncology",

issn = "1569-8041",

publisher = "Elsevier Ltd.",

number = "9",

}

Millstein, J, Budden, T, Goode, EL, Anglesio, MS, Talhouk, A, Intermaggio, MP, Leong, HS, Chen, S, Elatre, W, Gilks, B, Nazeran, T, Volchek, M, Bentley, RC, Wang, C, Chiu, DS, Kommoss, S, Leung, SCY, Senz, J, Lum, A, Chow, V, Sudderuddin, H, Mackenzie, R, George, J, Fereday, S, Hendley, J, Traficante, N, Steed, H, Koziak, JM, Köbel, M, McNeish, IA, Goranova, T, Ennis, D, Macintyre, G, Silva De Silva, D, Ramón y Cajal, T, García-Donas, J, Hernando Polo, S, Rodriguez, GC, Cushing-Haugen, KL, Harris, HR, Greene, CS, Zelaya, RA, Behrens, S, Fortner, RT, Sinn, P, Herpel, E, Lester, J, Lubiński, J, Oszurek, O, Tołoczko, A, Cybulski, C, Menkiszak, J, Pearce, CL, Pike, MC, Tseng, C, Alsop, J, Rhenius, V, Song, H, Jimenez-Linan, M, Piskorz, AM, Gentry-Maharaj, A, Karpinskyj, C, Widschwendter, M, Singh, N, Kennedy, CJ, Sharma, R & et al. 2020, 'Prognostic gene expression signature for high-grade serous ovarian cancer', Annals of Oncology, vol. 31, no. 9, pp. 1240-1250. https://doi.org/10.1016/j.annonc.2020.05.019

TY - JOUR

T1 - Prognostic gene expression signature for high-grade serous ovarian cancer

AU - Millstein, J.

AU - Budden, T.

AU - Goode, E. L.

AU - Anglesio, M. S.

AU - Talhouk, A.

AU - Intermaggio, M. P.

AU - Leong, H. S.

AU - Chen, S.

AU - Elatre, W.

AU - Gilks, B.

AU - Nazeran, T.

AU - Volchek, M.

AU - Bentley, R. C.

AU - Wang, C.

AU - Chiu, D. S.

AU - Kommoss, S.

AU - Leung, S. C. Y.

AU - Senz, J.

AU - Lum, A.

AU - Chow, V.

AU - Sudderuddin, H.

AU - Mackenzie, R.

AU - George, J.

AU - Fereday, S.

AU - Hendley, J.

AU - Traficante, N.

AU - Steed, H.

AU - Koziak, J. M.

AU - Köbel, M.

AU - McNeish, I. A.

AU - Goranova, T.

AU - Ennis, D.

AU - Macintyre, G.

AU - Silva De Silva, D.

AU - Ramón y Cajal, T.

AU - García-Donas, J.

AU - Hernando Polo, S.

AU - Rodriguez, G. C.

AU - Cushing-Haugen, K. L.

AU - Harris, H. R.

AU - Greene, C. S.

AU - Zelaya, R. A.

AU - Behrens, S.

AU - Fortner, R. T.

AU - Sinn, P.

AU - Herpel, E.

AU - Lester, J.

AU - Lubiński, J.

AU - Oszurek, O.

AU - Tołoczko, A.

AU - Cybulski, C.

AU - Menkiszak, J.

AU - Pearce, C. L.

AU - Pike, M. C.

AU - Tseng, C.

AU - Alsop, J.

AU - Rhenius, V.

AU - Song, H.

AU - Jimenez-Linan, M.

AU - Piskorz, A. M.

AU - Gentry-Maharaj, A.

AU - Karpinskyj, C.

AU - Widschwendter, M.

AU - Singh, N.

AU - Kennedy, C. J.

AU - Sharma, R.

AU - et al., null

PY - 2020/9/1

Y1 - 2020/9/1

N2 - Background: Median overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is ∼4 years, yet survival varies widely between patients. There are no well-established, gene expression signatures associated with prognosis. The aim of this study was to develop a robust prognostic signature for OS in patients with HGSOC. Patients and methods: Expression of 513 genes, selected from a meta-analysis of 1455 tumours and other candidates, was measured using NanoString technology from formalin-fixed paraffin-embedded tumour tissue collected from 3769 women with HGSOC from multiple studies. Elastic net regularization for survival analysis was applied to develop a prognostic model for 5-year OS, trained on 2702 tumours from 15 studies and evaluated on an independent set of 1067 tumours from six studies. Results: Expression levels of 276 genes were associated with OS (false discovery rate < 0.05) in covariate-adjusted single-gene analyses. The top five genes were TAP1, ZFHX4, CXCL9, FBN1 and PTGER3 (P < 0.001). The best performing prognostic signature included 101 genes enriched in pathways with treatment implications. Each gain of one standard deviation in the gene expression score conferred a greater than twofold increase in risk of death [hazard ratio (HR) 2.35, 95% confidence interval (CI) 2.02–2.71; P < 0.001]. Median survival [HR (95% CI)] by gene expression score quintile was 9.5 (8.3 to –), 5.4 (4.6–7.0), 3.8 (3.3–4.6), 3.2 (2.9–3.7) and 2.3 (2.1–2.6) years. Conclusion: The OTTA-SPOT (Ovarian Tumor Tissue Analysis consortium - Stratified Prognosis of Ovarian Tumours) gene expression signature may improve risk stratification in clinical trials by identifying patients who are least likely to achieve 5-year survival. The identified novel genes associated with the outcome may also yield opportunities for the development of targeted therapeutic approaches.

AB - Background: Median overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is ∼4 years, yet survival varies widely between patients. There are no well-established, gene expression signatures associated with prognosis. The aim of this study was to develop a robust prognostic signature for OS in patients with HGSOC. Patients and methods: Expression of 513 genes, selected from a meta-analysis of 1455 tumours and other candidates, was measured using NanoString technology from formalin-fixed paraffin-embedded tumour tissue collected from 3769 women with HGSOC from multiple studies. Elastic net regularization for survival analysis was applied to develop a prognostic model for 5-year OS, trained on 2702 tumours from 15 studies and evaluated on an independent set of 1067 tumours from six studies. Results: Expression levels of 276 genes were associated with OS (false discovery rate < 0.05) in covariate-adjusted single-gene analyses. The top five genes were TAP1, ZFHX4, CXCL9, FBN1 and PTGER3 (P < 0.001). The best performing prognostic signature included 101 genes enriched in pathways with treatment implications. Each gain of one standard deviation in the gene expression score conferred a greater than twofold increase in risk of death [hazard ratio (HR) 2.35, 95% confidence interval (CI) 2.02–2.71; P < 0.001]. Median survival [HR (95% CI)] by gene expression score quintile was 9.5 (8.3 to –), 5.4 (4.6–7.0), 3.8 (3.3–4.6), 3.2 (2.9–3.7) and 2.3 (2.1–2.6) years. Conclusion: The OTTA-SPOT (Ovarian Tumor Tissue Analysis consortium - Stratified Prognosis of Ovarian Tumours) gene expression signature may improve risk stratification in clinical trials by identifying patients who are least likely to achieve 5-year survival. The identified novel genes associated with the outcome may also yield opportunities for the development of targeted therapeutic approaches.

KW - cancer

KW - gene expression

KW - ovaries

KW - prognosis

UR - https://hdl.handle.net/1959.7/uws:57681

U2 - 10.1016/j.annonc.2020.05.019

DO - 10.1016/j.annonc.2020.05.019

M3 - Article

SN - 1569-8041

SN - 0923-7534

VL - 31

SP - 1240

EP - 1250

JO - Annals of Oncology

JF - Annals of Oncology

IS - 9

ER -

Prognostic gene expression signature for high-grade serous ovarian cancer

Abstract

Bibliographical note

Open Access - Access Right Statement

UN SDGs

Keywords

Access to Document

Other files and links

Fingerprint

Cite this