Risk prediction for late-stage ovarian cancer by meta-analysis of 1525 patient samples
Ovarian cancer causes more than 15000 deaths per year in the United States. The survival of patients is quite heterogeneous, and accurate prognostic tools would help with the clinical management of these patients. We developed and validated two gene expression signatures, the first for predicting su...
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| Vydáno v: | JNCI : Journal of the National Cancer Institute Ročník 106; číslo 5 |
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| Hlavní autoři: | , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
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United States
03.04.2014
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| ISSN: | 1460-2105, 1460-2105 |
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| Abstract | Ovarian cancer causes more than 15000 deaths per year in the United States. The survival of patients is quite heterogeneous, and accurate prognostic tools would help with the clinical management of these patients.
We developed and validated two gene expression signatures, the first for predicting survival in advanced-stage, serous ovarian cancer and the second for predicting debulking status. We integrated 13 publicly available datasets totaling 1525 subjects. We trained prediction models using a meta-analysis variation on the compound covariable method, tested models by a "leave-one-dataset-out" procedure, and validated models in additional independent datasets. Selected genes from the debulking signature were validated by immunohistochemistry and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) in two further independent cohorts of 179 and 78 patients, respectively. All statistical tests were two-sided.
The survival signature stratified patients into high- and low-risk groups (hazard ratio = 2.19; 95% confidence interval [CI] = 1.84 to 2.61) statistically significantly better than the TCGA signature (P = .04). POSTN, CXCL14, FAP, NUAK1, PTCH1, and TGFBR2 were validated by qRT-PCR (P < .05) and POSTN, CXCL14, and phosphorylated Smad2/3 were validated by immunohistochemistry (P < .001) as independent predictors of debulking status. The sum of immunohistochemistry intensities for these three proteins provided a tool that classified 92.8% of samples correctly in high- and low-risk groups for suboptimal debulking (area under the curve = 0.89; 95% CI = 0.84 to 0.93).
Our survival signature provides the most accurate and validated prognostic model for early- and advanced-stage high-grade, serous ovarian cancer. The debulking signature accurately predicts the outcome of cytoreductive surgery, potentially allowing for stratification of patients for primary vs secondary cytoreduction. |
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| AbstractList | Ovarian cancer causes more than 15000 deaths per year in the United States. The survival of patients is quite heterogeneous, and accurate prognostic tools would help with the clinical management of these patients.BACKGROUNDOvarian cancer causes more than 15000 deaths per year in the United States. The survival of patients is quite heterogeneous, and accurate prognostic tools would help with the clinical management of these patients.We developed and validated two gene expression signatures, the first for predicting survival in advanced-stage, serous ovarian cancer and the second for predicting debulking status. We integrated 13 publicly available datasets totaling 1525 subjects. We trained prediction models using a meta-analysis variation on the compound covariable method, tested models by a "leave-one-dataset-out" procedure, and validated models in additional independent datasets. Selected genes from the debulking signature were validated by immunohistochemistry and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) in two further independent cohorts of 179 and 78 patients, respectively. All statistical tests were two-sided.METHODSWe developed and validated two gene expression signatures, the first for predicting survival in advanced-stage, serous ovarian cancer and the second for predicting debulking status. We integrated 13 publicly available datasets totaling 1525 subjects. We trained prediction models using a meta-analysis variation on the compound covariable method, tested models by a "leave-one-dataset-out" procedure, and validated models in additional independent datasets. Selected genes from the debulking signature were validated by immunohistochemistry and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) in two further independent cohorts of 179 and 78 patients, respectively. All statistical tests were two-sided.The survival signature stratified patients into high- and low-risk groups (hazard ratio = 2.19; 95% confidence interval [CI] = 1.84 to 2.61) statistically significantly better than the TCGA signature (P = .04). POSTN, CXCL14, FAP, NUAK1, PTCH1, and TGFBR2 were validated by qRT-PCR (P < .05) and POSTN, CXCL14, and phosphorylated Smad2/3 were validated by immunohistochemistry (P < .001) as independent predictors of debulking status. The sum of immunohistochemistry intensities for these three proteins provided a tool that classified 92.8% of samples correctly in high- and low-risk groups for suboptimal debulking (area under the curve = 0.89; 95% CI = 0.84 to 0.93).RESULTSThe survival signature stratified patients into high- and low-risk groups (hazard ratio = 2.19; 95% confidence interval [CI] = 1.84 to 2.61) statistically significantly better than the TCGA signature (P = .04). POSTN, CXCL14, FAP, NUAK1, PTCH1, and TGFBR2 were validated by qRT-PCR (P < .05) and POSTN, CXCL14, and phosphorylated Smad2/3 were validated by immunohistochemistry (P < .001) as independent predictors of debulking status. The sum of immunohistochemistry intensities for these three proteins provided a tool that classified 92.8% of samples correctly in high- and low-risk groups for suboptimal debulking (area under the curve = 0.89; 95% CI = 0.84 to 0.93).Our survival signature provides the most accurate and validated prognostic model for early- and advanced-stage high-grade, serous ovarian cancer. The debulking signature accurately predicts the outcome of cytoreductive surgery, potentially allowing for stratification of patients for primary vs secondary cytoreduction.CONCLUSIONSOur survival signature provides the most accurate and validated prognostic model for early- and advanced-stage high-grade, serous ovarian cancer. The debulking signature accurately predicts the outcome of cytoreductive surgery, potentially allowing for stratification of patients for primary vs secondary cytoreduction. Ovarian cancer causes more than 15000 deaths per year in the United States. The survival of patients is quite heterogeneous, and accurate prognostic tools would help with the clinical management of these patients. We developed and validated two gene expression signatures, the first for predicting survival in advanced-stage, serous ovarian cancer and the second for predicting debulking status. We integrated 13 publicly available datasets totaling 1525 subjects. We trained prediction models using a meta-analysis variation on the compound covariable method, tested models by a "leave-one-dataset-out" procedure, and validated models in additional independent datasets. Selected genes from the debulking signature were validated by immunohistochemistry and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) in two further independent cohorts of 179 and 78 patients, respectively. All statistical tests were two-sided. The survival signature stratified patients into high- and low-risk groups (hazard ratio = 2.19; 95% confidence interval [CI] = 1.84 to 2.61) statistically significantly better than the TCGA signature (P = .04). POSTN, CXCL14, FAP, NUAK1, PTCH1, and TGFBR2 were validated by qRT-PCR (P < .05) and POSTN, CXCL14, and phosphorylated Smad2/3 were validated by immunohistochemistry (P < .001) as independent predictors of debulking status. The sum of immunohistochemistry intensities for these three proteins provided a tool that classified 92.8% of samples correctly in high- and low-risk groups for suboptimal debulking (area under the curve = 0.89; 95% CI = 0.84 to 0.93). Our survival signature provides the most accurate and validated prognostic model for early- and advanced-stage high-grade, serous ovarian cancer. The debulking signature accurately predicts the outcome of cytoreductive surgery, potentially allowing for stratification of patients for primary vs secondary cytoreduction. |
| Author | Oliva, Esther Culhane, Aedin C Birrer, Michael J Riester, Markus Waldron, Levi Michor, Franziska Wei, Wei Huttenhower, Curtis Kim, Sung-Hoon Trippa, Lorenzo Parmigiani, Giovanni |
| Author_xml | – sequence: 1 givenname: Markus surname: Riester fullname: Riester, Markus organization: Affiliations of authors: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA (MR, ACC, LT, FM, CH, GP); Department of Biostatistics, Harvard School of Public Health, Boston, MA (MR, ACC, LT, FM, CH, GP); Center for Cancer Research (WW, S-hK, MB) and Department of Pathology (EO), Massachusetts General Hospital, Boston, MA; City University of New York School of Public Health, Hunter College, New York, NY (LW); Sung-hoon Kim, Yonsei University College of Medicine, Seoul, Korea (S-HK) – sequence: 2 givenname: Wei surname: Wei fullname: Wei, Wei organization: Affiliations of authors: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA (MR, ACC, LT, FM, CH, GP); Department of Biostatistics, Harvard School of Public Health, Boston, MA (MR, ACC, LT, FM, CH, GP); Center for Cancer Research (WW, S-hK, MB) and Department of Pathology (EO), Massachusetts General Hospital, Boston, MA; City University of New York School of Public Health, Hunter College, New York, NY (LW); Sung-hoon Kim, Yonsei University College of Medicine, Seoul, Korea (S-HK) – sequence: 3 givenname: Levi surname: Waldron fullname: Waldron, Levi organization: Affiliations of authors: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA (MR, ACC, LT, FM, CH, GP); Department of Biostatistics, Harvard School of Public Health, Boston, MA (MR, ACC, LT, FM, CH, GP); Center for Cancer Research (WW, S-hK, MB) and Department of Pathology (EO), Massachusetts General Hospital, Boston, MA; City University of New York School of Public Health, Hunter College, New York, NY (LW); Sung-hoon Kim, Yonsei University College of Medicine, Seoul, Korea (S-HK) – sequence: 4 givenname: Aedin C surname: Culhane fullname: Culhane, Aedin C organization: Affiliations of authors: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA (MR, ACC, LT, FM, CH, GP); Department of Biostatistics, Harvard School of Public Health, Boston, MA (MR, ACC, LT, FM, CH, GP); Center for Cancer Research (WW, S-hK, MB) and Department of Pathology (EO), Massachusetts General Hospital, Boston, MA; City University of New York School of Public Health, Hunter College, New York, NY (LW); Sung-hoon Kim, Yonsei University College of Medicine, Seoul, Korea (S-HK) – sequence: 5 givenname: Lorenzo surname: Trippa fullname: Trippa, Lorenzo organization: Affiliations of authors: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA (MR, ACC, LT, FM, CH, GP); Department of Biostatistics, Harvard School of Public Health, Boston, MA (MR, ACC, LT, FM, CH, GP); Center for Cancer Research (WW, S-hK, MB) and Department of Pathology (EO), Massachusetts General Hospital, Boston, MA; City University of New York School of Public Health, Hunter College, New York, NY (LW); Sung-hoon Kim, Yonsei University College of Medicine, Seoul, Korea (S-HK) – sequence: 6 givenname: Esther surname: Oliva fullname: Oliva, Esther organization: Affiliations of authors: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA (MR, ACC, LT, FM, CH, GP); Department of Biostatistics, Harvard School of Public Health, Boston, MA (MR, ACC, LT, FM, CH, GP); Center for Cancer Research (WW, S-hK, MB) and Department of Pathology (EO), Massachusetts General Hospital, Boston, MA; City University of New York School of Public Health, Hunter College, New York, NY (LW); Sung-hoon Kim, Yonsei University College of Medicine, Seoul, Korea (S-HK) – sequence: 7 givenname: Sung-Hoon surname: Kim fullname: Kim, Sung-Hoon organization: Affiliations of authors: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA (MR, ACC, LT, FM, CH, GP); Department of Biostatistics, Harvard School of Public Health, Boston, MA (MR, ACC, LT, FM, CH, GP); Center for Cancer Research (WW, S-hK, MB) and Department of Pathology (EO), Massachusetts General Hospital, Boston, MA; City University of New York School of Public Health, Hunter College, New York, NY (LW); Sung-hoon Kim, Yonsei University College of Medicine, Seoul, Korea (S-HK) – sequence: 8 givenname: Franziska surname: Michor fullname: Michor, Franziska organization: Affiliations of authors: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA (MR, ACC, LT, FM, CH, GP); Department of Biostatistics, Harvard School of Public Health, Boston, MA (MR, ACC, LT, FM, CH, GP); Center for Cancer Research (WW, S-hK, MB) and Department of Pathology (EO), Massachusetts General Hospital, Boston, MA; City University of New York School of Public Health, Hunter College, New York, NY (LW); Sung-hoon Kim, Yonsei University College of Medicine, Seoul, Korea (S-HK) – sequence: 9 givenname: Curtis surname: Huttenhower fullname: Huttenhower, Curtis organization: Affiliations of authors: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA (MR, ACC, LT, FM, CH, GP); Department of Biostatistics, Harvard School of Public Health, Boston, MA (MR, ACC, LT, FM, CH, GP); Center for Cancer Research (WW, S-hK, MB) and Department of Pathology (EO), Massachusetts General Hospital, Boston, MA; City University of New York School of Public Health, Hunter College, New York, NY (LW); Sung-hoon Kim, Yonsei University College of Medicine, Seoul, Korea (S-HK) – sequence: 10 givenname: Giovanni surname: Parmigiani fullname: Parmigiani, Giovanni organization: Affiliations of authors: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA (MR, ACC, LT, FM, CH, GP); Department of Biostatistics, Harvard School of Public Health, Boston, MA (MR, ACC, LT, FM, CH, GP); Center for Cancer Research (WW, S-hK, MB) and Department of Pathology (EO), Massachusetts General Hospital, Boston, MA; City University of New York School of Public Health, Hunter College, New York, NY (LW); Sung-hoon Kim, Yonsei University College of Medicine, Seoul, Korea (S-HK) – sequence: 11 givenname: Michael J surname: Birrer fullname: Birrer, Michael J email: mbirrer@partners.org organization: Affiliations of authors: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA (MR, ACC, LT, FM, CH, GP); Department of Biostatistics, Harvard School of Public Health, Boston, MA (MR, ACC, LT, FM, CH, GP); Center for Cancer Research (WW, S-hK, MB) and Department of Pathology (EO), Massachusetts General Hospital, Boston, MA; City University of New York School of Public Health, Hunter College, New York, NY (LW); Sung-hoon Kim, Yonsei University College of Medicine, Seoul, Korea (S-HK). mbirrer@partners.org |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/24700803$$D View this record in MEDLINE/PubMed |
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| PublicationTitle | JNCI : Journal of the National Cancer Institute |
| PublicationTitleAlternate | J Natl Cancer Inst |
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| Snippet | Ovarian cancer causes more than 15000 deaths per year in the United States. The survival of patients is quite heterogeneous, and accurate prognostic tools... |
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| SubjectTerms | Female Humans Neoplasm Staging Oligonucleotide Array Sequence Analysis Ovarian Neoplasms - genetics Ovarian Neoplasms - mortality Ovarian Neoplasms - pathology Predictive Value of Tests Transcriptome United States - epidemiology |
| Title | Risk prediction for late-stage ovarian cancer by meta-analysis of 1525 patient samples |
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