Epigenetic-related gene mutations serve as potential biomarkers for immune checkpoint inhibitors in microsatellite-stable colorectal cancer
BackgroundCombination therapy with immune checkpoint inhibitors (ICIs) may benefit approximately 10-20% of microsatellite-stable colorectal cancer (MSS-CRC) patients. However, there is a lack of optimal biomarkers. This study aims to understand the predictive value of epigenetic-related gene mutatio...
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| Format: | Article |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1039631/full |
| _version_ | 1797984015308816384 |
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| author | Chao Liu Chao Liu Chao Liu Huiting Xiao Luying Cui Luying Cui Luying Cui Lin Fang Lin Fang Lin Fang Shuling Han Shuling Han Shuling Han Yuli Ruan Yuli Ruan Yuli Ruan Wenyuan Zhao Yanqiao Zhang Yanqiao Zhang Yanqiao Zhang Yanqiao Zhang |
| author_facet | Chao Liu Chao Liu Chao Liu Huiting Xiao Luying Cui Luying Cui Luying Cui Lin Fang Lin Fang Lin Fang Shuling Han Shuling Han Shuling Han Yuli Ruan Yuli Ruan Yuli Ruan Wenyuan Zhao Yanqiao Zhang Yanqiao Zhang Yanqiao Zhang Yanqiao Zhang |
| author_sort | Chao Liu |
| collection | DOAJ |
| description | BackgroundCombination therapy with immune checkpoint inhibitors (ICIs) may benefit approximately 10-20% of microsatellite-stable colorectal cancer (MSS-CRC) patients. However, there is a lack of optimal biomarkers. This study aims to understand the predictive value of epigenetic-related gene mutations in ICIs therapy in MSS-CRC patients.MethodsWe analyzed DNA sequences and gene expression profiles from The Cancer Genome Atlas (TCGA) to examine their immunological features. The Harbin Medical University Cancer Hospital (HMUCH) clinical cohort of MSS-CRC patients was used to validate the efficacy of ICIs in patients with epigenetic-related gene mutations (Epigenetic_Mut).ResultsIn TCGA, 18.35% of MSS-CRC patients (78/425) had epigenetic-related gene mutations. The Epigenetic_Mut group had a higher tumor mutation burden (TMB) and frameshift mutation (FS_mut) rates. In all MSS-CRC samples, Epigenetic_Mut was elevated in the immune subtype (CMS1) and had a strong correlation with immunological features. Epigenetic_Mut was also associated with favorable clinical outcomes in MSS-CRC patients receiving anti-PD-1-based therapy from the HMUCH cohort. Using immunohistochemistry and flow cytometry, we demonstrated that Epigenetic_Mut samples were associated with increased anti-tumor immune cells both in tumor tissues and peripheral blood.ConclusionMSS-CRC patients with epigenetic regulation impairment exhibit an immunologically active environment and may be more susceptible to treatment strategies based on ICIs. |
| first_indexed | 2024-04-11T06:55:02Z |
| format | Article |
| id | doaj.art-da2b368cb911443eb89ee985eec03567 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T06:55:02Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-da2b368cb911443eb89ee985eec035672022-12-22T04:39:03ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-11-011310.3389/fimmu.2022.10396311039631Epigenetic-related gene mutations serve as potential biomarkers for immune checkpoint inhibitors in microsatellite-stable colorectal cancerChao Liu0Chao Liu1Chao Liu2Huiting Xiao3Luying Cui4Luying Cui5Luying Cui6Lin Fang7Lin Fang8Lin Fang9Shuling Han10Shuling Han11Shuling Han12Yuli Ruan13Yuli Ruan14Yuli Ruan15Wenyuan Zhao16Yanqiao Zhang17Yanqiao Zhang18Yanqiao Zhang19Yanqiao Zhang20Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, ChinaClinical Research Center for Colorectal Cancer in Heilongjiang, Harbin Medical University Cancer Hospital, Harbin, ChinaKey Laboratory of Tumor Immunology in Heilongjiang, Harbin Medical University Cancer Hospital, Harbin, ChinaCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin, ChinaDepartment of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, ChinaClinical Research Center for Colorectal Cancer in Heilongjiang, Harbin Medical University Cancer Hospital, Harbin, ChinaKey Laboratory of Tumor Immunology in Heilongjiang, Harbin Medical University Cancer Hospital, Harbin, ChinaDepartment of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, ChinaClinical Research Center for Colorectal Cancer in Heilongjiang, Harbin Medical University Cancer Hospital, Harbin, ChinaKey Laboratory of Tumor Immunology in Heilongjiang, Harbin Medical University Cancer Hospital, Harbin, ChinaDepartment of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, ChinaClinical Research Center for Colorectal Cancer in Heilongjiang, Harbin Medical University Cancer Hospital, Harbin, ChinaKey Laboratory of Tumor Immunology in Heilongjiang, Harbin Medical University Cancer Hospital, Harbin, ChinaDepartment of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, ChinaClinical Research Center for Colorectal Cancer in Heilongjiang, Harbin Medical University Cancer Hospital, Harbin, ChinaKey Laboratory of Tumor Immunology in Heilongjiang, Harbin Medical University Cancer Hospital, Harbin, ChinaCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin, ChinaDepartment of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, ChinaClinical Research Center for Colorectal Cancer in Heilongjiang, Harbin Medical University Cancer Hospital, Harbin, ChinaKey Laboratory of Tumor Immunology in Heilongjiang, Harbin Medical University Cancer Hospital, Harbin, ChinaTranslational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, ChinaBackgroundCombination therapy with immune checkpoint inhibitors (ICIs) may benefit approximately 10-20% of microsatellite-stable colorectal cancer (MSS-CRC) patients. However, there is a lack of optimal biomarkers. This study aims to understand the predictive value of epigenetic-related gene mutations in ICIs therapy in MSS-CRC patients.MethodsWe analyzed DNA sequences and gene expression profiles from The Cancer Genome Atlas (TCGA) to examine their immunological features. The Harbin Medical University Cancer Hospital (HMUCH) clinical cohort of MSS-CRC patients was used to validate the efficacy of ICIs in patients with epigenetic-related gene mutations (Epigenetic_Mut).ResultsIn TCGA, 18.35% of MSS-CRC patients (78/425) had epigenetic-related gene mutations. The Epigenetic_Mut group had a higher tumor mutation burden (TMB) and frameshift mutation (FS_mut) rates. In all MSS-CRC samples, Epigenetic_Mut was elevated in the immune subtype (CMS1) and had a strong correlation with immunological features. Epigenetic_Mut was also associated with favorable clinical outcomes in MSS-CRC patients receiving anti-PD-1-based therapy from the HMUCH cohort. Using immunohistochemistry and flow cytometry, we demonstrated that Epigenetic_Mut samples were associated with increased anti-tumor immune cells both in tumor tissues and peripheral blood.ConclusionMSS-CRC patients with epigenetic regulation impairment exhibit an immunologically active environment and may be more susceptible to treatment strategies based on ICIs.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1039631/fullimmune checkpoint inhibitor therapybiomarkermicrosatellite-stablecolorectal cancerepigenetic-related gene mutations |
| spellingShingle | Chao Liu Chao Liu Chao Liu Huiting Xiao Luying Cui Luying Cui Luying Cui Lin Fang Lin Fang Lin Fang Shuling Han Shuling Han Shuling Han Yuli Ruan Yuli Ruan Yuli Ruan Wenyuan Zhao Yanqiao Zhang Yanqiao Zhang Yanqiao Zhang Yanqiao Zhang Epigenetic-related gene mutations serve as potential biomarkers for immune checkpoint inhibitors in microsatellite-stable colorectal cancer Frontiers in Immunology immune checkpoint inhibitor therapy biomarker microsatellite-stable colorectal cancer epigenetic-related gene mutations |
| title | Epigenetic-related gene mutations serve as potential biomarkers for immune checkpoint inhibitors in microsatellite-stable colorectal cancer |
| title_full | Epigenetic-related gene mutations serve as potential biomarkers for immune checkpoint inhibitors in microsatellite-stable colorectal cancer |
| title_fullStr | Epigenetic-related gene mutations serve as potential biomarkers for immune checkpoint inhibitors in microsatellite-stable colorectal cancer |
| title_full_unstemmed | Epigenetic-related gene mutations serve as potential biomarkers for immune checkpoint inhibitors in microsatellite-stable colorectal cancer |
| title_short | Epigenetic-related gene mutations serve as potential biomarkers for immune checkpoint inhibitors in microsatellite-stable colorectal cancer |
| title_sort | epigenetic related gene mutations serve as potential biomarkers for immune checkpoint inhibitors in microsatellite stable colorectal cancer |
| topic | immune checkpoint inhibitor therapy biomarker microsatellite-stable colorectal cancer epigenetic-related gene mutations |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1039631/full |
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