KMT2A/C mutations function as a potential predictive biomarker for immunotherapy in solid tumors
Abstract Epigenetic factors play important roles in tumor immunology. Histone-lysine N-methyltransferase 2 (KMT2) family genes exert histone H3 methylation, but its role in immunotherapy remains unclear. Our study is the first to investigate the correlation between KMT2 gene mutations and the clinic...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2020-12-01
|
| Series: | Biomarker Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40364-020-00241-0 |
| _version_ | 1818594695784169472 |
|---|---|
| author | Rui Zhang Hao-Xiang Wu Ming Xu Xiaoyan Xie |
| author_facet | Rui Zhang Hao-Xiang Wu Ming Xu Xiaoyan Xie |
| author_sort | Rui Zhang |
| collection | DOAJ |
| description | Abstract Epigenetic factors play important roles in tumor immunology. Histone-lysine N-methyltransferase 2 (KMT2) family genes exert histone H3 methylation, but its role in immunotherapy remains unclear. Our study is the first to investigate the correlation between KMT2 gene mutations and the clinical benefit of immune checkpoint inhibitors (ICI) treatment. We firstly collected a primary ICI-treated cohort (n = 546) and found that patients with KMT2A/C mutations yielded better prognosis in terms of progression-free survival (PFS, Hazard ratio [HR] = 0.66, P = 0.002), objective response rate (ORR, 40.9% vs 20.3%, P < 0.001), durable clinical benefit (DCB, 48.3% vs 29.8%, P = 0.001) and overall survival (OS, HR = 0.70, P = 0.033). Furthermore, we validated the predictive potential of KMT2A/C mutations in an expanded ICI-treated cohort (n = 1395). KMT2A/C-mutant patients achieved better OS compared with KMT2A/C-wildtype patients (HR = 0.68, P = 0.003); and the survival advantages appeared in the majority of cancer subtypes. Our study suggests that KMT2A/C mutations function as a novel and potential predictive biomarker for ICI treatment in multiple solid tumors and the underlying mechanism is worth investigating. |
| first_indexed | 2024-12-16T11:04:13Z |
| format | Article |
| id | doaj.art-8d7947db6927441ba5d0287b4c4fde80 |
| institution | Directory Open Access Journal |
| issn | 2050-7771 |
| language | English |
| last_indexed | 2024-12-16T11:04:13Z |
| publishDate | 2020-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Biomarker Research |
| spelling | doaj.art-8d7947db6927441ba5d0287b4c4fde802022-12-21T22:33:55ZengBMCBiomarker Research2050-77712020-12-01811510.1186/s40364-020-00241-0KMT2A/C mutations function as a potential predictive biomarker for immunotherapy in solid tumorsRui Zhang0Hao-Xiang Wu1Ming Xu2Xiaoyan Xie3Department of Medical Ultrasound, Division of Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-sen UniversityDepartment of Clinical Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer CenterDepartment of Medical Ultrasound, Division of Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-sen UniversityDepartment of Medical Ultrasound, Division of Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-sen UniversityAbstract Epigenetic factors play important roles in tumor immunology. Histone-lysine N-methyltransferase 2 (KMT2) family genes exert histone H3 methylation, but its role in immunotherapy remains unclear. Our study is the first to investigate the correlation between KMT2 gene mutations and the clinical benefit of immune checkpoint inhibitors (ICI) treatment. We firstly collected a primary ICI-treated cohort (n = 546) and found that patients with KMT2A/C mutations yielded better prognosis in terms of progression-free survival (PFS, Hazard ratio [HR] = 0.66, P = 0.002), objective response rate (ORR, 40.9% vs 20.3%, P < 0.001), durable clinical benefit (DCB, 48.3% vs 29.8%, P = 0.001) and overall survival (OS, HR = 0.70, P = 0.033). Furthermore, we validated the predictive potential of KMT2A/C mutations in an expanded ICI-treated cohort (n = 1395). KMT2A/C-mutant patients achieved better OS compared with KMT2A/C-wildtype patients (HR = 0.68, P = 0.003); and the survival advantages appeared in the majority of cancer subtypes. Our study suggests that KMT2A/C mutations function as a novel and potential predictive biomarker for ICI treatment in multiple solid tumors and the underlying mechanism is worth investigating.https://doi.org/10.1186/s40364-020-00241-0BiomarkerImmune checkpoint inhibitorsKMT2A/CPan-cancer analysis |
| spellingShingle | Rui Zhang Hao-Xiang Wu Ming Xu Xiaoyan Xie KMT2A/C mutations function as a potential predictive biomarker for immunotherapy in solid tumors Biomarker Research Biomarker Immune checkpoint inhibitors KMT2A/C Pan-cancer analysis |
| title | KMT2A/C mutations function as a potential predictive biomarker for immunotherapy in solid tumors |
| title_full | KMT2A/C mutations function as a potential predictive biomarker for immunotherapy in solid tumors |
| title_fullStr | KMT2A/C mutations function as a potential predictive biomarker for immunotherapy in solid tumors |
| title_full_unstemmed | KMT2A/C mutations function as a potential predictive biomarker for immunotherapy in solid tumors |
| title_short | KMT2A/C mutations function as a potential predictive biomarker for immunotherapy in solid tumors |
| title_sort | kmt2a c mutations function as a potential predictive biomarker for immunotherapy in solid tumors |
| topic | Biomarker Immune checkpoint inhibitors KMT2A/C Pan-cancer analysis |
| url | https://doi.org/10.1186/s40364-020-00241-0 |
| work_keys_str_mv | AT ruizhang kmt2acmutationsfunctionasapotentialpredictivebiomarkerforimmunotherapyinsolidtumors AT haoxiangwu kmt2acmutationsfunctionasapotentialpredictivebiomarkerforimmunotherapyinsolidtumors AT mingxu kmt2acmutationsfunctionasapotentialpredictivebiomarkerforimmunotherapyinsolidtumors AT xiaoyanxie kmt2acmutationsfunctionasapotentialpredictivebiomarkerforimmunotherapyinsolidtumors |