Julia Maria Ressler, Erwin Tomasich, Teresa Hatziioannou, Helmut Ringl, Gerwin Heller, Rita Silmbrod, Lynn Gottmann, Angelika Martina Starzer, Nina Zila, Philipp Tschandl, Christoph Hoeller, Matthias Preusser, Anna Sophie Berghoff
{"title":"DNA甲基化特征与转移性黑色素瘤对免疫检查点抑制剂的反应相关","authors":"Julia Maria Ressler, Erwin Tomasich, Teresa Hatziioannou, Helmut Ringl, Gerwin Heller, Rita Silmbrod, Lynn Gottmann, Angelika Martina Starzer, Nina Zila, Philipp Tschandl, Christoph Hoeller, Matthias Preusser, Anna Sophie Berghoff","doi":"10.1007/s11523-024-01041-4","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>DNA methylation profiles have emerged as potential predictors of therapeutic response in various solid tumors.</p><p><strong>Objective: </strong>This study aimed to analyze the DNA methylation profiles of patients with stage IV metastatic melanoma undergoing first-line immune checkpoint inhibitor treatment and evaluate their correlation with a radiological response according to immune-related Response Evaluation Criteria in Solid Tumors (iRECIST).</p><p><strong>Methods: </strong>A total of 81 tissue samples from 71 patients with metastatic melanoma (27 female, 44 male) were included in this study. We utilized Illumina Methylation EPIC Beadchips to retrieve their genome-wide methylation profile by interrogating >850,000 CpG sites. Clustering based on the 500 most differentially methylated genes was conducted to identify distinct methylation patterns associated with immune checkpoint inhibitor response. Results were further aligned with an independent, previously published data set.</p><p><strong>Results: </strong>The median progression-free survival was 8.5 months (range: 0-104.1 months), and the median overall survival was 30.6 months (range: 0-104.1 months). Objective responses were observed in 29 patients (40.8%). DNA methylation profiling revealed specific signatures that correlated with radiological response to immune checkpoint inhibitors. Three distinct clusters were identified based on the methylation patterns of the 500 most differentially methylated genes. Cluster 1 (12/12) and cluster 2 (12/24) exhibited a higher proportion of responders, while cluster 3 (39/45) predominantly consisted of non-responders. In the validation data set, responders also showed more frequent hypomethylation although differences in the data sets limit the interpretation.</p><p><strong>Conclusions: </strong>These findings suggest that DNA methylation profiling of tumor tissues might serve as a predictive biomarker for immune checkpoint inhibitor response in patients with metastatic melanoma. Further validation studies are warranted to confirm the efficiency of DNA methylation profiling as a predictive tool in the context of immunotherapy for metastatic melanoma.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"263-275"},"PeriodicalIF":4.4000,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10963567/pdf/","citationCount":"0","resultStr":"{\"title\":\"DNA Methylation Signatures Correlate with Response to Immune Checkpoint Inhibitors in Metastatic Melanoma.\",\"authors\":\"Julia Maria Ressler, Erwin Tomasich, Teresa Hatziioannou, Helmut Ringl, Gerwin Heller, Rita Silmbrod, Lynn Gottmann, Angelika Martina Starzer, Nina Zila, Philipp Tschandl, Christoph Hoeller, Matthias Preusser, Anna Sophie Berghoff\",\"doi\":\"10.1007/s11523-024-01041-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>DNA methylation profiles have emerged as potential predictors of therapeutic response in various solid tumors.</p><p><strong>Objective: </strong>This study aimed to analyze the DNA methylation profiles of patients with stage IV metastatic melanoma undergoing first-line immune checkpoint inhibitor treatment and evaluate their correlation with a radiological response according to immune-related Response Evaluation Criteria in Solid Tumors (iRECIST).</p><p><strong>Methods: </strong>A total of 81 tissue samples from 71 patients with metastatic melanoma (27 female, 44 male) were included in this study. We utilized Illumina Methylation EPIC Beadchips to retrieve their genome-wide methylation profile by interrogating >850,000 CpG sites. Clustering based on the 500 most differentially methylated genes was conducted to identify distinct methylation patterns associated with immune checkpoint inhibitor response. Results were further aligned with an independent, previously published data set.</p><p><strong>Results: </strong>The median progression-free survival was 8.5 months (range: 0-104.1 months), and the median overall survival was 30.6 months (range: 0-104.1 months). Objective responses were observed in 29 patients (40.8%). DNA methylation profiling revealed specific signatures that correlated with radiological response to immune checkpoint inhibitors. Three distinct clusters were identified based on the methylation patterns of the 500 most differentially methylated genes. Cluster 1 (12/12) and cluster 2 (12/24) exhibited a higher proportion of responders, while cluster 3 (39/45) predominantly consisted of non-responders. In the validation data set, responders also showed more frequent hypomethylation although differences in the data sets limit the interpretation.</p><p><strong>Conclusions: </strong>These findings suggest that DNA methylation profiling of tumor tissues might serve as a predictive biomarker for immune checkpoint inhibitor response in patients with metastatic melanoma. 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DNA Methylation Signatures Correlate with Response to Immune Checkpoint Inhibitors in Metastatic Melanoma.
Background: DNA methylation profiles have emerged as potential predictors of therapeutic response in various solid tumors.
Objective: This study aimed to analyze the DNA methylation profiles of patients with stage IV metastatic melanoma undergoing first-line immune checkpoint inhibitor treatment and evaluate their correlation with a radiological response according to immune-related Response Evaluation Criteria in Solid Tumors (iRECIST).
Methods: A total of 81 tissue samples from 71 patients with metastatic melanoma (27 female, 44 male) were included in this study. We utilized Illumina Methylation EPIC Beadchips to retrieve their genome-wide methylation profile by interrogating >850,000 CpG sites. Clustering based on the 500 most differentially methylated genes was conducted to identify distinct methylation patterns associated with immune checkpoint inhibitor response. Results were further aligned with an independent, previously published data set.
Results: The median progression-free survival was 8.5 months (range: 0-104.1 months), and the median overall survival was 30.6 months (range: 0-104.1 months). Objective responses were observed in 29 patients (40.8%). DNA methylation profiling revealed specific signatures that correlated with radiological response to immune checkpoint inhibitors. Three distinct clusters were identified based on the methylation patterns of the 500 most differentially methylated genes. Cluster 1 (12/12) and cluster 2 (12/24) exhibited a higher proportion of responders, while cluster 3 (39/45) predominantly consisted of non-responders. In the validation data set, responders also showed more frequent hypomethylation although differences in the data sets limit the interpretation.
Conclusions: These findings suggest that DNA methylation profiling of tumor tissues might serve as a predictive biomarker for immune checkpoint inhibitor response in patients with metastatic melanoma. Further validation studies are warranted to confirm the efficiency of DNA methylation profiling as a predictive tool in the context of immunotherapy for metastatic melanoma.
期刊介绍：
Targeted Oncology addresses physicians and scientists committed to oncology and cancer research by providing a programme of articles on molecularly targeted pharmacotherapy in oncology. The journal includes:
Original Research Articles on all aspects of molecularly targeted agents for the treatment of cancer, including immune checkpoint inhibitors and related approaches.
Comprehensive narrative Review Articles and shorter Leading Articles discussing relevant clinically established as well as emerging agents and pathways.
Current Opinion articles that place interesting areas in perspective.
Therapy in Practice articles that provide a guide to the optimum management of a condition and highlight practical, clinically relevant considerations and recommendations.
Systematic Reviews that use explicit, systematic methods as outlined by the PRISMA statement.
Adis Drug Reviews of the properties and place in therapy of both newer and established targeted drugs in oncology.
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