TET1 mutations as a predictive biomarker for immune checkpoint inhibitors in colon adenocarcinoma
Abstract Background The ten-eleven translocation 1 (TET1), which is essential for active DNA demethylation, plays a multifaceted role in the pathogenesis of colorectal cancer. The study has demonstrated the association of TET1 mutations with a high response to immune checkpoint inhibitors (ICIs) in...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-04-01
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| Series: | World Journal of Surgical Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12957-022-02581-7 |
| _version_ | 1819209905724194816 |
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| author | Tianzhu Qiu Xiaoxuan Wang Furong Du Xiangjing Hu Fujun Sun Chao Song Jie Zhao |
| author_facet | Tianzhu Qiu Xiaoxuan Wang Furong Du Xiangjing Hu Fujun Sun Chao Song Jie Zhao |
| author_sort | Tianzhu Qiu |
| collection | DOAJ |
| description | Abstract Background The ten-eleven translocation 1 (TET1), which is essential for active DNA demethylation, plays a multifaceted role in the pathogenesis of colorectal cancer. The study has demonstrated the association of TET1 mutations with a high response to immune checkpoint inhibitors (ICIs) in diverse cancers. However, the relationship between TET1 mutations and the response to ICIs in colon cancer is still lacking. Methods The prognosis, predictive markers, immune characteristics, mutation number of DNA damage repair (DDR) pathways, pathway enrichment, and drug sensitivity conditions were all compared between TET1-mutated and wild-type patients with colon adenocarcinoma (COAD). Results The overall survival of patients with TET1 mutations in the ICI-treated cohort was significantly longer than those without (p = 0.0059). Compared with the wild-type patients, TET1-mutated patients had higher tumor mutational burden and neoantigen load, enhanced abundance of tumor-infiltrating immune cells, increased expression of immune-related genes, and mutation number of DDR pathways. Additionally, the patients with TET1 mutations were found to be more sensitive to lapatinib and 5-fluorouracil. Conclusion These findings suggest that TET1 mutations may serve as a potential biomarker for the response to ICIs in COAD patients. |
| first_indexed | 2024-12-23T06:02:43Z |
| format | Article |
| id | doaj.art-6b6bac97165e4077a76c2ddebf2fcd50 |
| institution | Directory Open Access Journal |
| issn | 1477-7819 |
| language | English |
| last_indexed | 2024-12-23T06:02:43Z |
| publishDate | 2022-04-01 |
| publisher | BMC |
| record_format | Article |
| series | World Journal of Surgical Oncology |
| spelling | doaj.art-6b6bac97165e4077a76c2ddebf2fcd502022-12-21T17:57:38ZengBMCWorld Journal of Surgical Oncology1477-78192022-04-0120111110.1186/s12957-022-02581-7TET1 mutations as a predictive biomarker for immune checkpoint inhibitors in colon adenocarcinomaTianzhu Qiu0Xiaoxuan Wang1Furong Du2Xiangjing Hu3Fujun Sun4Chao Song5Jie Zhao6Department of Oncology, The First Affiliated Hospital of Nanjing Medical UniversityState Key Laboratory of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd.State Key Laboratory of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd.State Key Laboratory of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd.State Key Laboratory of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd.State Key Laboratory of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd.Henan Key Laboratory of Precision MedicineAbstract Background The ten-eleven translocation 1 (TET1), which is essential for active DNA demethylation, plays a multifaceted role in the pathogenesis of colorectal cancer. The study has demonstrated the association of TET1 mutations with a high response to immune checkpoint inhibitors (ICIs) in diverse cancers. However, the relationship between TET1 mutations and the response to ICIs in colon cancer is still lacking. Methods The prognosis, predictive markers, immune characteristics, mutation number of DNA damage repair (DDR) pathways, pathway enrichment, and drug sensitivity conditions were all compared between TET1-mutated and wild-type patients with colon adenocarcinoma (COAD). Results The overall survival of patients with TET1 mutations in the ICI-treated cohort was significantly longer than those without (p = 0.0059). Compared with the wild-type patients, TET1-mutated patients had higher tumor mutational burden and neoantigen load, enhanced abundance of tumor-infiltrating immune cells, increased expression of immune-related genes, and mutation number of DDR pathways. Additionally, the patients with TET1 mutations were found to be more sensitive to lapatinib and 5-fluorouracil. Conclusion These findings suggest that TET1 mutations may serve as a potential biomarker for the response to ICIs in COAD patients.https://doi.org/10.1186/s12957-022-02581-7Colon adenocarcinomaTen-eleven translocation 1Immune checkpoint inhibitorsOverall survivalPredictive biomarker |
| spellingShingle | Tianzhu Qiu Xiaoxuan Wang Furong Du Xiangjing Hu Fujun Sun Chao Song Jie Zhao TET1 mutations as a predictive biomarker for immune checkpoint inhibitors in colon adenocarcinoma World Journal of Surgical Oncology Colon adenocarcinoma Ten-eleven translocation 1 Immune checkpoint inhibitors Overall survival Predictive biomarker |
| title | TET1 mutations as a predictive biomarker for immune checkpoint inhibitors in colon adenocarcinoma |
| title_full | TET1 mutations as a predictive biomarker for immune checkpoint inhibitors in colon adenocarcinoma |
| title_fullStr | TET1 mutations as a predictive biomarker for immune checkpoint inhibitors in colon adenocarcinoma |
| title_full_unstemmed | TET1 mutations as a predictive biomarker for immune checkpoint inhibitors in colon adenocarcinoma |
| title_short | TET1 mutations as a predictive biomarker for immune checkpoint inhibitors in colon adenocarcinoma |
| title_sort | tet1 mutations as a predictive biomarker for immune checkpoint inhibitors in colon adenocarcinoma |
| topic | Colon adenocarcinoma Ten-eleven translocation 1 Immune checkpoint inhibitors Overall survival Predictive biomarker |
| url | https://doi.org/10.1186/s12957-022-02581-7 |
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