DNA methylation-based immune response signature improves patient diagnosis in multiple cancers
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE72308 | GEO | 2017/07/16
SECONDARY ACCESSION(S): PRJNA293700
REPOSITORIES: GEO
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Project description:The tumor immune response is increasingly associated with better clinical outcomes in breast and other cancers. However, the evaluation of tumor-infiltrating lymphocytes (TILs) relies on histopathological measurements with limited accuracy and reproducibility. Here, we profiled DNA methylation markers to identify a methylation of TIL (MeTIL) signature that recapitulates TIL evaluations and their prognostic value for long-term outcomes in breast cancer (BC).MeTIL signature scores were correlated with clinical endpoints reflecting overall or disease-free survival and a pathologic complete response to preoperative anthracycline therapy in 3 BC cohorts from the Jules Bordet Institute in Brussels and in other cancer types from The Cancer Genome Atlas.The MeTIL signature measured TIL distributions in a sensitive manner and predicted survival and response to chemotherapy in BC better than did histopathological assessment of TILs or gene expression-based immune markers, respectively. The MeTIL signature also improved the prediction of survival in other malignancies, including melanoma and lung cancer. Furthermore, the MeTIL signature predicted differences in survival for malignancies in which TILs were not known to have a prognostic value. Finally, we showed that MeTIL markers can be determined by bisulfite pyrosequencing of small amounts of DNA from formalin-fixed, paraffin-embedded tumor tissue, supporting clinical applications for this methodology.This study highlights the power of DNA methylation to evaluate tumor immune responses and the potential of this approach to improve the diagnosis and treatment of breast and other cancers.This work was funded by the Fonds National de la Recherche Scientifique (FNRS) and Télévie, the INNOVIRIS Brussels Region BRUBREAST Project, the IUAP P7/03 program, the Belgian "Foundation against Cancer," the Breast Cancer Research Foundation (BCRF), and the Fonds Gaston Ithier.
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Project description:Breast cancer (BC) is one of the most common and deadliest malignancies in women worldwide. Tumor immune response is increasingly recognized to be associated with better clinical outcome in breast and other cancers. However, the quantitative evaluation of the tumor immune response by measuring tumor-infiltrating lymphocytes (TILs) remains challenging, since it relies on subjective measurements, which are limited in accuracy and reproducibility. In this study, we sought to identify a set of DNA methylation markers (MeTIL signature) that better recapitulate the evaluation of TILs and their impact on long-term outcome in BC. We showed that the MeTIL score measures TIL distributions in a more robust and sensitive manner than conventional pathological TIL counts and that this translates into better prediction of survival and response to chemotherapy in BC. We demonstrated that the MeTIL score can be determined in low amounts of DNA from FFPE tumor tissue by bisulfite pyrosequencing allowing for the fast and cost-efficient evaluation of TILs in the clinical setting.
2017-07-16 | GSE72245 | GEO
Project description:Breast cancer (BC) is one of the most common and deadliest malignancies in women worldwide. Tumor immune response is increasingly recognized to be associated with better clinical outcome in breast and other cancers. However, the quantitative evaluation of the tumor immune response by measuring tumor-infiltrating lymphocytes (TILs) remains challenging, since it relies on subjective measurements, which are limited in accuracy and reproducibility. In this study, we sought to identify a set of DNA methylation markers (MeTIL signature) that better recapitulate the evaluation of TILs and their impact on long-term outcome in BC. We showed that the MeTIL score measures TIL distributions in a more robust and sensitive manner than conventional pathological TIL counts and that this translates into better prediction of survival and response to chemotherapy in BC. We demonstrated that the MeTIL score can be determined in low amounts of DNA from FFPE tumor tissue by bisulfite pyrosequencing allowing for the fast and cost-efficient evaluation of TILs in the clinical setting.
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Project description:Breast cancer (BC) is one of the most common and deadliest malignancies in women worldwide. Tumor immune response is increasingly recognized to be associated with better clinical outcome in breast and other cancers. However, the quantitative evaluation of the tumor immune response by measuring tumor-infiltrating lymphocytes (TILs) remains challenging, since it relies on subjective measurements, which are limited in accuracy and reproducibility. In this study, we sought to identify a set of DNA methylation markers (MeTIL signature) that better recapitulate the evaluation of TILs and their impact on long-term outcome in BC. We showed that the MeTIL score measures TIL distributions in a more robust and sensitive manner than conventional pathological TIL counts and that this translates into better prediction of survival and response to chemotherapy in BC. We demonstrated that the MeTIL score can be determined in low amounts of DNA from FFPE tumor tissue by bisulfite pyrosequencing allowing for the fast and cost-efficient evaluation of TILs in the clinical setting.
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