Project description:To date, a variety of studies have employed gene expression profiling to classify ovarian carcinomas in clinically relevant subtypes. These studies provided valuable first clues to molecular changes in ovarian cancer that might be exploited in new treatment strategies. However, most studies were of relatively limited size and the number of overlapping genes in the identified profiles was minimal. Although identification of gene expression profiles associated with clinically relevant subtypes in ovarian cancer is important, knowledge is now emerging rapidly on how genes interact in pathways, networks and complexes; this allows us to unravel those cellular pathways determining the biological behavior of ovarian cancer, that might be successfully targeted with drugs. The aim of our study was: 1) To develop a gene expression profile associated with overall survival in advanced stage serous ovarian cancer, 2) to assess the association of pathways and transcription factors with overall survival, and 3) to validate our identified profile and pathways/transcription factors in an independent set of ovarian cancers. According to a randomized design, profiling of 157 advanced stage serous ovarian cancers was performed in duplicate using ~35K 70-mer oligonucleotide microarrays. A continuous predictor of overall survival was built taking into account well-known issues in microarray analysis, such as multiple testing and overfitting. A functional class scoring analysis was utilized to assess pathways/transcription factors for their association with overall survival. The prognostic value of genes that constitute our overall survival profile was validated on a fully independent, publicly available data set of 118 well-defined primary serous ovarian cancers. Furthermore, functional class scoring analysis was also performed on this independent data set to assess the similarities with results from our own data set. An 86-gene overall survival profile discriminated between patients with unfavorable and favorable prognosis (median survival, 19 vs. 41 months, respectively; permutation p-value of log-rank statistic = 0.015) and maintained its independent prognostic value in multivariate analysis. Genes that comprised the overall survival profile were also able to discriminate between the two risk groups in the independent data set. In our dataset 17/167 pathways and 13/111 transcription factors were associated with overall survival of which 16 and 12 respectively were confirmed in the independent dataset. Our study provides new clues to genes, pathways and transcription factors which contribute to the clinical outcome of serous ovarian cancer and might be exploited in designing new treatment strategies. Keywords: Oncology/Gynecological Cancers, Genetics and Genomics/Cancer Genetics, Genetics and Genomics/Gene Expression, Genetics and Genomics/Genomics

Project description:To date, a variety of studies have employed gene expression profiling to classify ovarian carcinomas in clinically relevant subtypes. These studies provided valuable first clues to molecular changes in ovarian cancer that might be exploited in new treatment strategies. However, most studies were of relatively limited size and the number of overlapping genes in the identified profiles was minimal. Although identification of gene expression profiles associated with clinically relevant subtypes in ovarian cancer is important, knowledge is now emerging rapidly on how genes interact in pathways, networks and complexes; this allows us to unravel those cellular pathways determining the biological behavior of ovarian cancer, that might be successfully targeted with drugs. The aim of our study was: 1) To develop a gene expression profile associated with overall survival in advanced stage serous ovarian cancer, 2) to assess the association of pathways and transcription factors with overall survival, and 3) to validate our identified profile and pathways/transcription factors in an independent set of ovarian cancers. According to a randomized design, profiling of 157 advanced stage serous ovarian cancers was performed in duplicate using ~35K 70-mer oligonucleotide microarrays. A continuous predictor of overall survival was built taking into account well-known issues in microarray analysis, such as multiple testing and overfitting. A functional class scoring analysis was utilized to assess pathways/transcription factors for their association with overall survival. The prognostic value of genes that constitute our overall survival profile was validated on a fully independent, publicly available data set of 118 well-defined primary serous ovarian cancers. Furthermore, functional class scoring analysis was also performed on this independent data set to assess the similarities with results from our own data set. An 86-gene overall survival profile discriminated between patients with unfavorable and favorable prognosis (median survival, 19 vs. 41 months, respectively; permutation p-value of log-rank statistic = 0.015) and maintained its independent prognostic value in multivariate analysis. Genes that comprised the overall survival profile were also able to discriminate between the two risk groups in the independent data set. In our dataset 17/167 pathways and 13/111 transcription factors were associated with overall survival of which 16 and 12 respectively were confirmed in the independent dataset. Our study provides new clues to genes, pathways and transcription factors which contribute to the clinical outcome of serous ovarian cancer and might be exploited in designing new treatment strategies. Keywords: Oncology/Gynecological Cancers, Genetics and Genomics/Cancer Genetics, Genetics and Genomics/Gene Expression, Genetics and Genomics/Genomics According to a randomized design, profiling of 157 advanced stage serous ovarian cancers was performed in duplicate using ~35K 70-mer oligonucleotide microarrays. Two randomly selected samples were hybridized together on the arrays for intensity-based instead of ratio-based analysis of the microarray data.

Dataset Information

Survival-related profile, pathways, and transcription factors in ovarian cancer.

Background

Methods and findings

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