| Title: |
Prognostic gene expression signature for high-grade serous ovarian cancer |
| Authors: |
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; AOCS Group; Fereday, S; Hendley, J; Traficante, N; Steed, H; Koziak, JM; Köbel, M; McNeish, IA; Goranova, T; Ennis, D; Macintyre, G; Silva, D; Ramón Y Cajal, T; García-Donas, J; Polo, SH; 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, A; 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; A deFazio; Gayther, SA; García, MJ; Henderson, M; 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 |
| Source: |
Annals of Oncology (2020) (In press). |
| Publication Year: |
2020 |
| Collection: |
University College London: UCL Discovery |
| Subject Terms: |
formalin fixed paraffin embedded; gene expression; high grade serous ovarian cancer; overall survival; prognosis |
| Description: |
Background: Median overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is approximately four 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 overall survival in HGSOC patients. Patients and methods: Expression of 513 genes, selected from a meta-analysis of 1455 tumours and other candidates, were measured using NanoString technology from formalin-fixed, paraffin-embedded (FFPE) tumour tissue from 3,769 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 fifteen 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 (FDR) < 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 (GES) conferred a greater than two-fold increase in risk of death [HR = 2.35 (2.02, 2.71); P < 0.001]. Median survival by GES quintile was 9.5 (8.3, --), 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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10099729/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10099729/1/1-s2.0-S0923753420398410-main.pdf; https://discovery.ucl.ac.uk/id/eprint/10099729/ |
| Rights: |
open |
| Accession Number: |
edsbas.606056F3 |
| Database: |
BASE |