Document Type
Article
Publication Date
9-2020
Keywords
JGM, Cystadenocarcinoma, Serous, Female, Humans, Ovarian Neoplasms, Prognosis, Proportional Hazards Models, Survival Analysis, Transcriptome
JAX Source
Ann Oncol 2020 Sep; 31(9):1240-1250
Volume
31
Issue
9
First Page
1240
Last Page
1250
ISSN
1569-8041
PMID
32473302
DOI
https://doi.org/10.1016/j.annonc.2020.05.019
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.
Recommended Citation
Millstein J,
Budden T,
Goode E,
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Talhouk A,
Intermaggio M,
Leong H,
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Elatre W,
Gilks B,
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Silva De Silva D,
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García-Donas J,
Hernando Polo S,
Rodriguez G,
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Harris H,
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Zelaya R,
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Fortner R,
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Oszurek O,
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Winterhoff B,
Slamon D,
Levine D,
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Chang-Claude J,
Gronwald J,
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Goodman M,
Schildkraut J,
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Chenevix-Trench G,
deFazio A,
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Konecny G,
Huntsman D,
Bowtell D,
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Prognostic gene expression signature for high-grade serous ovarian cancer. Ann Oncol 2020 Sep; 31(9):1240-1250
Comments
This is an open access article under the CC BY-NC-ND license.