Development and validation of a gene-based model for outcome prediction in germ cell tumors using a combined genomic and expression profiling approach Journal Article
| Authors: | Korkola, J. E.; Heck, S.; Olshen, A. B.; Feldman, D. R.; Reuter, V. E.; Houldsworth, J.; Bosl, G. J.; Chaganti, R. S. K. |
| Article Title: | Development and validation of a gene-based model for outcome prediction in germ cell tumors using a combined genomic and expression profiling approach |
| Abstract: | Germ Cell Tumors (GCT) have a high cure rate, but we currently lack the ability to accurately identify the small subset of patients who will die from their disease. We used a combined genomic and expression profiling approach to identify genomic regions and underlying genes that are predictive of outcome in GCT patients. We performed arraybased comparative genomic hybridization (CGH) on 53 non-seminomatous GCTs (NSGCTs) treated with cisplatin based chemotherapy and defined altered genomic regions using Circular Binary Segmentation. We identified 14 regions associated with two year disease-free survival (2yDFS) and 16 regions associated with five year disease-specific survival (5yDSS). From corresponding expression data, we identified 101 probe sets that showed significant changes in expression. We built several models based on these differentially expressed genes, then tested them in an independent validation set of 54 NSGCTs. These predictive models correctly classified outcome in 64-79.6% of patients in the validation set, depending on the endpoint utilized. Survival analysis demonstrated a significant separation of patients with good versus poor predicted outcome when using a combined gene set model. Multivariate analysis using clinical risk classification with the combined gene model indicated that they were independent prognostic markers. This novel set of predictive genes from altered genomic regions is almost entirely independent of our previously identified set of predictive genes for patients with NSGCTs. These genes may aid in the identification of the small subset of patients who are at high risk of poor outcome. © 2015 Korkola et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| Keywords: | controlled study; human tissue; cisplatin; disease free survival; follow up; gene expression; gene expression profiling; gene identification; gene dosage; comparative genomic hybridization; disease specific survival; non seminomatous germinoma; cancer prognosis; human; article |
| Journal Title: | PLoS ONE |
| Volume: | 10 |
| Issue: | 12 |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Date Published: | 2015-12-01 |
| Start Page: | e0142846 |
| Language: | English |
| DOI: | 10.1371/journal.pone.0142846 |
| PROVIDER: | scopus |
| PMCID: | PMC4666461 |
| PUBMED: | 26624623 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 4 April 2016 -- Source: Scopus |
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