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; P R Harnett; B Gao; S E Johnatty; R Sayer; J Boros; S J Winham; G L Keeney; S H Kaufmann; M C Larson; H Luk; B Y Hernandez; P J Thompson; L R Wilkens; M E Carney; B Trabert; J Lissowska; L Brinton; M E Sherman; C Bodelon; S Hinsley; L A Lewsley; R Glasspool; S N Banerjee; E A Stronach; P Haluska; I Ray-Coquard; S Mahner; B Winterhoff; D Slamon; D A Levine; L E Kelemen; J Benitez; J Chang-Claude; J Gronwald; A H Wu; U Menon; M T Goodman; J M Schildkraut; N Wentzensen; R Brown; A Berchuck; G Chenevix-Trench; A deFazio; S A Gayther; M J García; M J Henderson; M A Rossing; A Beeghly-Fadiel; P A Fasching; S Orsulic; B Y Karlan; G E Konecny; D G Huntsman; D D Bowtell; J D Brenton; J A Doherty; P D P Pharoah; S J Ramus; AOCS study group

doi:10.1016/j.annonc.2020.05.019

Prognostic gene expression signature for high-grade serous ovarian cancer

Standard

Prognostic gene expression signature for high-grade serous ovarian cancer. / 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; Köbel, M; McNeish, I A; Goranova, T; Ennis, D; Macintyre, G; Silva De Silva, D; Ramón Y Cajal, T; García-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; Lubiński, J; Oszurek, O; Tołoczko, 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; García, 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; AOCS study group.

in: ANN ONCOL, Jahrgang 31, Nr. 9, 09.2020, S. 1240-1250.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

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, Harnett, PR, Gao, B, Johnatty, SE, Sayer, R, Boros, J, Winham, SJ, Keeney, GL, Kaufmann, SH, Larson, MC, Luk, H, Hernandez, BY, Thompson, PJ, Wilkens, LR, Carney, ME, Trabert, B, Lissowska, J, Brinton, L, Sherman, ME, Bodelon, C, Hinsley, S, Lewsley, LA, Glasspool, R, Banerjee, SN, Stronach, EA, Haluska, P, Ray-Coquard, I, Mahner, S, Winterhoff, B, Slamon, D, Levine, DA, Kelemen, LE, Benitez, J, Chang-Claude, J, Gronwald, J, Wu, AH, Menon, U, Goodman, MT, Schildkraut, JM, Wentzensen, N, Brown, R, Berchuck, A, Chenevix-Trench, G, deFazio, A, Gayther, SA, García, MJ, Henderson, MJ, Rossing, MA, Beeghly-Fadiel, A, Fasching, PA, Orsulic, S, Karlan, BY, Konecny, GE, Huntsman, DG, Bowtell, DD, Brenton, JD, Doherty, JA, Pharoah, PDP, Ramus, SJ & AOCS study group 2020, 'Prognostic gene expression signature for high-grade serous ovarian cancer', ANN ONCOL, Jg. 31, Nr. 9, S. 1240-1250. https://doi.org/10.1016/j.annonc.2020.05.019

APA

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., ... AOCS study group (2020). Prognostic gene expression signature for high-grade serous ovarian cancer. ANN ONCOL, 31(9), 1240-1250. https://doi.org/10.1016/j.annonc.2020.05.019

Vancouver

Millstein J, Budden T, Goode EL, Anglesio MS, Talhouk A, Intermaggio MP et al. Prognostic gene expression signature for high-grade serous ovarian cancer. ANN ONCOL. 2020 Sep;31(9):1240-1250. https://doi.org/10.1016/j.annonc.2020.05.019

Bibtex

@article{022e4db817ac4b6b90c3a563c367a80d,

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.",

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 Harnett, {P R} and B Gao and Johnatty, {S E} and R Sayer and J Boros and Winham, {S J} and Keeney, {G L} and Kaufmann, {S H} and Larson, {M C} and H Luk and Hernandez, {B Y} and Thompson, {P J} and Wilkens, {L R} and Carney, {M E} and B Trabert and J Lissowska and L Brinton and Sherman, {M E} and C Bodelon and S Hinsley and Lewsley, {L A} and R Glasspool and Banerjee, {S N} and Stronach, {E A} and P Haluska and I Ray-Coquard and S Mahner and B Winterhoff and D Slamon and Levine, {D A} and Kelemen, {L E} and J Benitez and J Chang-Claude and J Gronwald and Wu, {A H} and U Menon and Goodman, {M T} and Schildkraut, {J M} and N Wentzensen and R Brown and A Berchuck and G Chenevix-Trench and A deFazio and Gayther, {S A} and Garc{\'i}a, {M J} and Henderson, {M J} and Rossing, {M A} and A Beeghly-Fadiel and Fasching, {P A} and S Orsulic and Karlan, {B Y} and Konecny, {G E} and Huntsman, {D G} and Bowtell, {D D} and Brenton, {J D} and Doherty, {J A} and Pharoah, {P D P} and Ramus, {S J} and {AOCS study group}",

year = "2020",

month = sep,

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

language = "English",

volume = "31",

pages = "1240--1250",

journal = "ANN ONCOL",

issn = "0923-7534",

publisher = "Oxford University Press",

number = "9",

}

RIS

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 - Harnett, P R

AU - Gao, B

AU - Johnatty, S E

AU - Sayer, R

AU - Boros, J

AU - Winham, S J

AU - Keeney, G L

AU - Kaufmann, S H

AU - Larson, M C

AU - Luk, H

AU - Hernandez, B Y

AU - Thompson, P J

AU - Wilkens, L R

AU - Carney, M E

AU - Trabert, B

AU - Lissowska, J

AU - Brinton, L

AU - Sherman, M E

AU - Bodelon, C

AU - Hinsley, S

AU - Lewsley, L A

AU - Glasspool, R

AU - Banerjee, S N

AU - Stronach, E A

AU - Haluska, P

AU - Ray-Coquard, I

AU - Mahner, S

AU - Winterhoff, B

AU - Slamon, D

AU - Levine, D A

AU - Kelemen, L E

AU - Benitez, J

AU - Chang-Claude, J

AU - Gronwald, J

AU - Wu, A H

AU - Menon, U

AU - Goodman, M T

AU - Schildkraut, J M

AU - Wentzensen, N

AU - Brown, R

AU - Berchuck, A

AU - Chenevix-Trench, G

AU - deFazio, A

AU - Gayther, S A

AU - García, M J

AU - Henderson, M J

AU - Rossing, M A

AU - Beeghly-Fadiel, A

AU - Fasching, P A

AU - Orsulic, S

AU - Karlan, B Y

AU - Konecny, G E

AU - Huntsman, D G

AU - Bowtell, D D

AU - Brenton, J D

AU - Doherty, J A

AU - Pharoah, P D P

AU - Ramus, S J

AU - AOCS study group

PY - 2020/9

Y1 - 2020/9

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.

U2 - 10.1016/j.annonc.2020.05.019

DO - 10.1016/j.annonc.2020.05.019

M3 - SCORING: Journal article

C2 - 32473302

VL - 31

SP - 1240

EP - 1250

JO - ANN ONCOL

JF - ANN ONCOL

SN - 0923-7534

IS - 9

ER -