Cellular Histone Modification Patterns Predict Prognosis and Treatment Response in Resectable Pancreatic Adenocarcinoma: Results From RTOG 9704
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- Ananya Manuyakorn
- From the Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok Thailand; Radiation Therapy Oncology Group, Philadelphia, PA; Department of Medicine, Department of Pathology and Laboratory Medicine, and Department of Surgery, Jonsson Comprehensive Cancer Center; Departments of Human Genetics and Biostatistics in the School of Public Health; Department of Biological Chemistry; and Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen...
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- Rebecca Paulus
- From the Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok Thailand; Radiation Therapy Oncology Group, Philadelphia, PA; Department of Medicine, Department of Pathology and Laboratory Medicine, and Department of Surgery, Jonsson Comprehensive Cancer Center; Departments of Human Genetics and Biostatistics in the School of Public Health; Department of Biological Chemistry; and Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen...
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- James Farrell
- From the Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok Thailand; Radiation Therapy Oncology Group, Philadelphia, PA; Department of Medicine, Department of Pathology and Laboratory Medicine, and Department of Surgery, Jonsson Comprehensive Cancer Center; Departments of Human Genetics and Biostatistics in the School of Public Health; Department of Biological Chemistry; and Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen...
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- Nicole A. Dawson
- From the Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok Thailand; Radiation Therapy Oncology Group, Philadelphia, PA; Department of Medicine, Department of Pathology and Laboratory Medicine, and Department of Surgery, Jonsson Comprehensive Cancer Center; Departments of Human Genetics and Biostatistics in the School of Public Health; Department of Biological Chemistry; and Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen...
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- Sheila Tze
- From the Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok Thailand; Radiation Therapy Oncology Group, Philadelphia, PA; Department of Medicine, Department of Pathology and Laboratory Medicine, and Department of Surgery, Jonsson Comprehensive Cancer Center; Departments of Human Genetics and Biostatistics in the School of Public Health; Department of Biological Chemistry; and Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen...
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- Gardenia Cheung-Lau
- From the Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok Thailand; Radiation Therapy Oncology Group, Philadelphia, PA; Department of Medicine, Department of Pathology and Laboratory Medicine, and Department of Surgery, Jonsson Comprehensive Cancer Center; Departments of Human Genetics and Biostatistics in the School of Public Health; Department of Biological Chemistry; and Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen...
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- Oscar Joe Hines
- From the Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok Thailand; Radiation Therapy Oncology Group, Philadelphia, PA; Department of Medicine, Department of Pathology and Laboratory Medicine, and Department of Surgery, Jonsson Comprehensive Cancer Center; Departments of Human Genetics and Biostatistics in the School of Public Health; Department of Biological Chemistry; and Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen...
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- Howard Reber
- From the Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok Thailand; Radiation Therapy Oncology Group, Philadelphia, PA; Department of Medicine, Department of Pathology and Laboratory Medicine, and Department of Surgery, Jonsson Comprehensive Cancer Center; Departments of Human Genetics and Biostatistics in the School of Public Health; Department of Biological Chemistry; and Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen...
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- David B. Seligson
- From the Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok Thailand; Radiation Therapy Oncology Group, Philadelphia, PA; Department of Medicine, Department of Pathology and Laboratory Medicine, and Department of Surgery, Jonsson Comprehensive Cancer Center; Departments of Human Genetics and Biostatistics in the School of Public Health; Department of Biological Chemistry; and Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen...
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- Steve Horvath
- From the Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok Thailand; Radiation Therapy Oncology Group, Philadelphia, PA; Department of Medicine, Department of Pathology and Laboratory Medicine, and Department of Surgery, Jonsson Comprehensive Cancer Center; Departments of Human Genetics and Biostatistics in the School of Public Health; Department of Biological Chemistry; and Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen...
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- Siavash K. Kurdistani
- From the Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok Thailand; Radiation Therapy Oncology Group, Philadelphia, PA; Department of Medicine, Department of Pathology and Laboratory Medicine, and Department of Surgery, Jonsson Comprehensive Cancer Center; Departments of Human Genetics and Biostatistics in the School of Public Health; Department of Biological Chemistry; and Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen...
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- Chandhan Guha
- From the Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok Thailand; Radiation Therapy Oncology Group, Philadelphia, PA; Department of Medicine, Department of Pathology and Laboratory Medicine, and Department of Surgery, Jonsson Comprehensive Cancer Center; Departments of Human Genetics and Biostatistics in the School of Public Health; Department of Biological Chemistry; and Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen...
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- David W. Dawson
- From the Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok Thailand; Radiation Therapy Oncology Group, Philadelphia, PA; Department of Medicine, Department of Pathology and Laboratory Medicine, and Department of Surgery, Jonsson Comprehensive Cancer Center; Departments of Human Genetics and Biostatistics in the School of Public Health; Department of Biological Chemistry; and Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen...
Description
<jats:sec><jats:title>Purpose</jats:title><jats:p> Differences in cellular levels of histone modifications have predicted clinical outcome in certain cancers. Here, we studied the prognostic and predictive value of three histone modifications in pancreatic adenocarcinoma. </jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p> Tissue microarrays (TMAs) from two pancreatic adenocarcinoma cohorts were examined, including those from a 195-patient cohort from Radiation Therapy Oncology Group trial RTOG 9704, a multicenter, phase III, randomized treatment trial comparing adjuvant gemcitabine with fluorouracil and a 140-patient cohort of patients with stage I or II cancer from University of California, Los Angeles Medical Center. Immunohistochemistry was performed for histone H3 lysine 4 dimethylation (H3K4me2), histone H3 lysine 9 dimethylation (H3K9me2), and histone H3 lysine 18 acetylation (H3K18ac). Positive tumor cell staining for each histone modification was used to classify patients into low- and high-staining groups, which were related to clinicopathologic parameters and clinical outcome measures. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> Low cellular levels of H3K4me2, H3K9me2, or H3K18ac were each significant and independent predictors of poor survival in univariate and multivariate models, and combined low levels of H3K4me2 and/or H3K18ac were the most significant predictor of overall survival (hazard ratio, 2.93; 95% CI, 1.78 to 4.82) in the University of California, Los Angeles cohort. In subgroup analyses, histone levels were predictive of survival specifically for those patients with node-negative cancer or for those patients receiving adjuvant fluorouracil, but not gemcitabine, in RTOG 9704. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> Cellular levels of histone modifications define previously unrecognized subsets of patients with pancreatic adenocarcinoma with distinct epigenetic phenotypes and clinical outcomes and represent prognostic and predictive biomarkers that could inform clinical decisions, including the use of fluorouracil chemotherapy. </jats:p></jats:sec>
Journal
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- Journal of Clinical Oncology
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Journal of Clinical Oncology 28 (8), 1358-1365, 2010-03-10
American Society of Clinical Oncology (ASCO)
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Details 詳細情報について
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- CRID
- 1360292621296160640
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- ISSN
- 15277755
- 0732183X
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- Data Source
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- Crossref