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.; Chow, V.; Sudderuddin, H.; Mackenzie, R.; George, J.; Fereday, S.; Hendley, J.; Traficante, N.; Steed, H.; Koziak, J. M.; Kobel, M.; McNeish, I. A.; Goranova, T.; Ennis, D.; Macintyre, G.; De Silva, D. Silva; Ramon y Cajal, T.; Garcia-Donas, J.; Hernando Polo, S.; Rodriguez, G. C.; Cushing-Haugen, K. L.; Harris, H. R.; Greene, C. S.; Zelaya, R. A.; Behrens, S.; Fortner, R. T.; Sinn, P.; Herpel, E.; Lester, J.; Lubinski, J.; Oszurek, O.; Toloczko, A.; Cybulski, C.; Menkiszak, J.; Pearce, C. L.; Pike, M. C.; Tseng, C.; Alsop, J.; Rhenius, V.; Song, H.; Jimenez-Linan, M.; Piskorz, A. M.; Gentry-Maharaj, A.; Karpinskyj, C.; Widschwendter, M.; Singh, N.; Kennedy, C. J.; Sharma, R.; Harnett, P. R.; Gao, B.; Johnatty, S. E.; Sayer, R.; Boros, J.; Winham, S. J.; Keeney, G. L.; Kaufmann, S. H.; Larson, M. C.; Luk, H.; Hernandez, B. Y.; Thompson, P. J.; Wilkens, L. R.; Carney, M. E.; Trabert, B.; Lissowska, J.; Brinton, L.; Sherman, M. E.; Bodelon, C.; Hinsley, S.; Lewsley, L. A.; Glasspool, R.; Banerjee, S. N.; Stronach, E. A.; Haluska, P.; Ray-Coquard, I; Mahner, S.; Winterhoff, B.; Slamon, D.; Levine, D. A.; Kelemen, L. E.; Benitez, J.; Chang-Claude, J.; Gronwald, J.; Wu, A. H.; Menon, U.; Goodman, M. T.; Schildkraut, J. M.; Wentzensen, N.; Brown, R.; Berchuck, A.; Chenevix-Trench, G.; DeFazio, A.; Gayther, S. A.; Garcia, M. J.; Henderson, M. J.; Rossing, M. A.; Beeghly-Fadiel, A.; Fasching, P. A.; Orsulic, S.; Karlan, B. Y.; Konecny, G. E.; Huntsman, D. G.; Bowtell, D. D.; Brenton, J. D.; Doherty, J. A.; Pharoah, P. D. P.; Ramus, S. J. (2020): Prognostic gene expression signature for high-grade serous ovarian cancer. In: Annals of Oncology, Vol. 31, No. 9: pp. 1240-1250 |
Abstract
Background: Median overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is similar to 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.
Item Type: | Journal article |
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Faculties: | Medicine |
Subjects: | 600 Technology > 610 Medicine and health |
ISSN: | 0923-7534 |
Language: | English |
ID Code: | 85500 |
Deposited On: | 25. Jan 2022 09:14 |
Last Modified: | 25. Jan 2022 09:14 |
- BASE
- 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.
- Chow, V.
- Sudderuddin, H.
- Mackenzie, R.
- George, J.
- Fereday, S.
- Hendley, J.
- Traficante, N.
- Steed, H.
- Koziak, J. M.
- Kobel, M.
- McNeish, I. A.
- Goranova, T.
- Ennis, D.
- Macintyre, G.
- De Silva, D. Silva
- Ramon y Cajal, T.
- Garcia-Donas, J.
- Hernando Polo, S.
- Rodriguez, G. C.
- Cushing-Haugen, K. L.
- Harris, H. R.
- Greene, C. S.
- Zelaya, R. A.
- Behrens, S.
- Fortner, R. T.
- Sinn, P.
- Herpel, E.
- Lester, J.
- Lubinski, J.
- Oszurek, O.
- Toloczko, A.
- Cybulski, C.
- Menkiszak, J.
- Pearce, C. L.
- Pike, M. C.
- Tseng, C.
- Alsop, J.
- Rhenius, V.
- Song, H.
- Jimenez-Linan, M.
- Piskorz, A. M.
- Gentry-Maharaj, A.
- Karpinskyj, C.
- Widschwendter, M.
- Singh, N.
- Kennedy, C. J.
- Sharma, R.
- Harnett, P. R.
- Gao, B.
- Johnatty, S. E.
- Sayer, R.
- Boros, J.
- Winham, S. J.
- Keeney, G. L.
- Kaufmann, S. H.
- Larson, M. C.
- Luk, H.
- Hernandez, B. Y.
- Thompson, P. J.
- Wilkens, L. R.
- Carney, M. E.
- Trabert, B.
- Lissowska, J.
- Brinton, L.
- Sherman, M. E.
- Bodelon, C.
- Hinsley, S.
- Lewsley, L. A.
- Glasspool, R.
- Banerjee, S. N.
- Stronach, E. A.
- Haluska, P.
- Ray-Coquard, I
- Mahner, S.
- Winterhoff, B.
- Slamon, D.
- Levine, D. A.
- Kelemen, L. E.
- Benitez, J.
- Chang-Claude, J.
- Gronwald, J.
- Wu, A. H.
- Menon, U.
- Goodman, M. T.
- Schildkraut, J. M.
- Wentzensen, N.
- Brown, R.
- Berchuck, A.
- Chenevix-Trench, G.
- DeFazio, A.
- Gayther, S. A.
- Garcia, M. J.
- Henderson, M. J.
- Rossing, M. A.
- Beeghly-Fadiel, A.
- Fasching, P. A.
- Orsulic, S.
- Karlan, B. Y.
- Konecny, G. E.
- Huntsman, D. G.
- Bowtell, D. D.
- Brenton, J. D.
- Doherty, J. A.
- Pharoah, P. D. P.
- Ramus, S. J.
- Google Scholar
- 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.
- Chow, V.
- Sudderuddin, H.
- Mackenzie, R.
- George, J.
- Fereday, S.
- Hendley, J.
- Traficante, N.
- Steed, H.
- Koziak, J. M.
- Kobel, M.
- McNeish, I. A.
- Goranova, T.
- Ennis, D.
- Macintyre, G.
- De Silva, D. Silva
- Ramon y Cajal, T.
- Garcia-Donas, J.
- Hernando Polo, S.
- Rodriguez, G. C.
- Cushing-Haugen, K. L.
- Harris, H. R.
- Greene, C. S.
- Zelaya, R. A.
- Behrens, S.
- Fortner, R. T.
- Sinn, P.
- Herpel, E.
- Lester, J.
- Lubinski, J.
- Oszurek, O.
- Toloczko, A.
- Cybulski, C.
- Menkiszak, J.
- Pearce, C. L.
- Pike, M. C.
- Tseng, C.
- Alsop, J.
- Rhenius, V.
- Song, H.
- Jimenez-Linan, M.
- Piskorz, A. M.
- Gentry-Maharaj, A.
- Karpinskyj, C.
- Widschwendter, M.
- Singh, N.
- Kennedy, C. J.
- Sharma, R.
- Harnett, P. R.
- Gao, B.
- Johnatty, S. E.
- Sayer, R.
- Boros, J.
- Winham, S. J.
- Keeney, G. L.
- Kaufmann, S. H.
- Larson, M. C.
- Luk, H.
- Hernandez, B. Y.
- Thompson, P. J.
- Wilkens, L. R.
- Carney, M. E.
- Trabert, B.
- Lissowska, J.
- Brinton, L.
- Sherman, M. E.
- Bodelon, C.
- Hinsley, S.
- Lewsley, L. A.
- Glasspool, R.
- Banerjee, S. N.
- Stronach, E. A.
- Haluska, P.
- Ray-Coquard, I
- Mahner, S.
- Winterhoff, B.
- Slamon, D.
- Levine, D. A.
- Kelemen, L. E.
- Benitez, J.
- Chang-Claude, J.
- Gronwald, J.
- Wu, A. H.
- Menon, U.
- Goodman, M. T.
- Schildkraut, J. M.
- Wentzensen, N.
- Brown, R.
- Berchuck, A.
- Chenevix-Trench, G.
- DeFazio, A.
- Gayther, S. A.
- Garcia, M. J.
- Henderson, M. J.
- Rossing, M. A.
- Beeghly-Fadiel, A.
- Fasching, P. A.
- Orsulic, S.
- Karlan, B. Y.
- Konecny, G. E.
- Huntsman, D. G.
- Bowtell, D. D.
- Brenton, J. D.
- Doherty, J. A.
- Pharoah, P. D. P.
- Ramus, S. J.