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000156955 0247_ $$2doi$$a10.1016/j.annonc.2020.05.019
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000156955 1001_ $$aMillstein, J.$$b0
000156955 245__ $$aPrognostic gene expression signature for high-grade serous ovarian cancer.
000156955 260__ $$aOxford$$bOxford Univ. Press$$c2020
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000156955 500__ $$a2020 Sep;31(9):1240-1250
000156955 520__ $$aMedian 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.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.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.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.
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000156955 7001_ $$aBudden, T.$$b1
000156955 7001_ $$aGoode, E. L.$$b2
000156955 7001_ $$aAnglesio, M. S.$$b3
000156955 7001_ $$aTalhouk, A.$$b4
000156955 7001_ $$aIntermaggio, M. P.$$b5
000156955 7001_ $$aLeong, H. S.$$b6
000156955 7001_ $$aChen, S.$$b7
000156955 7001_ $$aElatre, W.$$b8
000156955 7001_ $$aGilks, B.$$b9
000156955 7001_ $$aNazeran, T.$$b10
000156955 7001_ $$aVolchek, M.$$b11
000156955 7001_ $$aBentley, R. C.$$b12
000156955 7001_ $$aWang, C.$$b13
000156955 7001_ $$aChiu, D. S.$$b14
000156955 7001_ $$aKommoss, S.$$b15
000156955 7001_ $$aLeung, S. C. Y.$$b16
000156955 7001_ $$aSenz, J.$$b17
000156955 7001_ $$aLum, A.$$b18
000156955 7001_ $$aChow, V.$$b19
000156955 7001_ $$aSudderuddin, H.$$b20
000156955 7001_ $$aMackenzie, R.$$b21
000156955 7001_ $$aGeorge, J.$$b22
000156955 7001_ $$aGroup, AOCS$$b23$$eCollaboration Author
000156955 7001_ $$aFereday, S.$$b24
000156955 7001_ $$aHendley, J.$$b25
000156955 7001_ $$aTraficante, N.$$b26
000156955 7001_ $$aSteed, H.$$b27
000156955 7001_ $$aKoziak, J. M.$$b28
000156955 7001_ $$aKöbel, M.$$b29
000156955 7001_ $$aMcNeish, I. A.$$b30
000156955 7001_ $$aGoranova, T.$$b31
000156955 7001_ $$aEnnis, D.$$b32
000156955 7001_ $$aMacintyre, G.$$b33
000156955 7001_ $$aSilva De Silva, D.$$b34
000156955 7001_ $$aRamón Y Cajal, T.$$b35
000156955 7001_ $$aGarcía-Donas, J.$$b36
000156955 7001_ $$aHernando Polo, S.$$b37
000156955 7001_ $$aRodriguez, G. C.$$b38
000156955 7001_ $$aCushing-Haugen, K. L.$$b39
000156955 7001_ $$aHarris, H. R.$$b40
000156955 7001_ $$aGreene, C. S.$$b41
000156955 7001_ $$aZelaya, R. A.$$b42
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000156955 7001_ $$aHerpel, E.$$b46
000156955 7001_ $$aLester, J.$$b47
000156955 7001_ $$aLubiński, J.$$b48
000156955 7001_ $$aOszurek, O.$$b49
000156955 7001_ $$aTołoczko, A.$$b50
000156955 7001_ $$aCybulski, C.$$b51
000156955 7001_ $$aMenkiszak, J.$$b52
000156955 7001_ $$aPearce, C. L.$$b53
000156955 7001_ $$aPike, M. C.$$b54
000156955 7001_ $$aTseng, C.$$b55
000156955 7001_ $$aAlsop, J.$$b56
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000156955 7001_ $$aPiskorz, A. M.$$b60
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000156955 7001_ $$aKarpinskyj, C.$$b62
000156955 7001_ $$aWidschwendter, M.$$b63
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000156955 7001_ $$aKennedy, C. J.$$b65
000156955 7001_ $$aSharma, R.$$b66
000156955 7001_ $$aHarnett, P. R.$$b67
000156955 7001_ $$aGao, B.$$b68
000156955 7001_ $$aJohnatty, S. E.$$b69
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000156955 7001_ $$aBoros, J.$$b71
000156955 7001_ $$aWinham, S. J.$$b72
000156955 7001_ $$aKeeney, G. L.$$b73
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000156955 7001_ $$aHernandez, B. Y.$$b77
000156955 7001_ $$aThompson, P. J.$$b78
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