A prognostic gene expression index in ovarian cancer - Validation across different independent data sets

Carsten Denkert, Jan Budczies, Silvia Darb-Esfahani, B. Györffy, Jalid Sehouli, Dominique Könsgen, Robert Zeillinger, Wilko Weichert, Aurelia Noske, Ann Christin Buckendahl, Berit M. Müller, Manfred Dietel, Hermann Lage

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Abstract

Ovarian carcinoma has the highest mortality rate among gynaecological malignancies. In this project, we investigated the hypothesis that molecular markers are able to predict outcome of ovarian cancer independently of classical clinical predictors, and that these molecular markers can be validated using independent data sets. We applied a semi-supervised method for prediction of patient survival. Microarrays from a cohort of 80 ovarian carcinomas (TOC cohort) were used for the development of a predictive model, which was then evaluated in an entirely independent cohort of 118 carcinomas (Duke cohort). A 300-gene ovarian prognostic index (OPI) was generated and validated in a leave-one-out approach in the TOC cohort (Kaplan-Meier analysis, p = 0.0087). In a second validation step, the prognostic power of the OPI was confirmed in an independent data set (Duke cohort, p = 0.0063). In multivariate analysis, the OPI was independent of the post-operative residual tumour, the main clinico-pathological prognostic parameter with an adjusted hazard ratio of 6.4 (TOC cohort, CI 1.8-23.5, p = 0.0049) and 1.9 (Duke cohort, CI 1.2-3.0, p = 0.0068). We constructed a combined score of molecular data (OPI) and clinical parameters (residual tumour), which was able to define patient groups with highly significant differences in survival. The integrated analysis of gene expression data as well as residual tumour can be used for optimized assessment of the prognosis of platinum-taxol-treated ovarian cancer. As traditional treatment options are limited, this analysis may be able to optimize clinical management and to identify those patients who would be candidates for new therapeutic strategies.

Original languageEnglish
Pages (from-to)273-280
Number of pages8
JournalJournal of Pathology
Volume218
Issue number2
DOIs
Publication statusPublished - Jun 2009

Fingerprint

Residual Neoplasm
Ovarian Neoplasms
Carcinoma
Gene Expression
Survival
Kaplan-Meier Estimate
Paclitaxel
Platinum
Multivariate Analysis
Mortality
Therapeutics
Genes
Datasets
Neoplasms

Keywords

  • Gene expression
  • Ovarian carcinoma
  • Prognosis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Denkert, C., Budczies, J., Darb-Esfahani, S., Györffy, B., Sehouli, J., Könsgen, D., ... Lage, H. (2009). A prognostic gene expression index in ovarian cancer - Validation across different independent data sets. Journal of Pathology, 218(2), 273-280. https://doi.org/10.1002/path.2547

A prognostic gene expression index in ovarian cancer - Validation across different independent data sets. / Denkert, Carsten; Budczies, Jan; Darb-Esfahani, Silvia; Györffy, B.; Sehouli, Jalid; Könsgen, Dominique; Zeillinger, Robert; Weichert, Wilko; Noske, Aurelia; Buckendahl, Ann Christin; Müller, Berit M.; Dietel, Manfred; Lage, Hermann.

In: Journal of Pathology, Vol. 218, No. 2, 06.2009, p. 273-280.

Research output: Contribution to journalArticle

Denkert, C, Budczies, J, Darb-Esfahani, S, Györffy, B, Sehouli, J, Könsgen, D, Zeillinger, R, Weichert, W, Noske, A, Buckendahl, AC, Müller, BM, Dietel, M & Lage, H 2009, 'A prognostic gene expression index in ovarian cancer - Validation across different independent data sets', Journal of Pathology, vol. 218, no. 2, pp. 273-280. https://doi.org/10.1002/path.2547
Denkert, Carsten ; Budczies, Jan ; Darb-Esfahani, Silvia ; Györffy, B. ; Sehouli, Jalid ; Könsgen, Dominique ; Zeillinger, Robert ; Weichert, Wilko ; Noske, Aurelia ; Buckendahl, Ann Christin ; Müller, Berit M. ; Dietel, Manfred ; Lage, Hermann. / A prognostic gene expression index in ovarian cancer - Validation across different independent data sets. In: Journal of Pathology. 2009 ; Vol. 218, No. 2. pp. 273-280.
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