A novel immune checkpoints-based signature to predict prognosis and response to immunotherapy in lung adenocarcinoma
Abstract Background Except for B7-CD28 family members, more novel immune checkpoints are being discovered. They are closely associated with tumor immune microenvironment and regulate the function of many immune cells. Various cancer therapeutic studies targeting these novel immune checkpoints are cu...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-07-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-022-03520-6 |
| _version_ | 1818501807979102208 |
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| author | Nan Sun Yuejun Luo Bo Zheng Zhihui Zhang Chaoqi Zhang Zhen Zhang Guochao Zhang Fengwei Tan Qi Xue Shugeng Gao Jie He |
| author_facet | Nan Sun Yuejun Luo Bo Zheng Zhihui Zhang Chaoqi Zhang Zhen Zhang Guochao Zhang Fengwei Tan Qi Xue Shugeng Gao Jie He |
| author_sort | Nan Sun |
| collection | DOAJ |
| description | Abstract Background Except for B7-CD28 family members, more novel immune checkpoints are being discovered. They are closely associated with tumor immune microenvironment and regulate the function of many immune cells. Various cancer therapeutic studies targeting these novel immune checkpoints are currently in full swing. However, studies concerning novel immune checkpoints phenotypes and clinical significance in lung adenocarcinoma (LUAD) are still limited. Methods We enrolled 1883 LUAD cases from nine different cohorts. The samples from The Cancer Genome Atlas (TCGA) were used as a training set, whereas seven microarray data cohorts and an independent cohort with 102 qPCR data were used for validation. The immune profiles and potential mechanism of the system were also explored. Results After univariate Cox proportional hazards regression and stepwise multivariable Cox analysis, a novel immune checkpoints-based system (LTA, CD160, and CD40LG) were identified from the training set, which significantly stratified patients into high- and low-risk groups with different survivals. Furthermore, this system has been well validated in different clinical subgroups and multiple validation cohorts. It also acted as an independent prognostic factor for patients with LAUD in different cohorts. Further exploration suggested that high-risk patients exhibited distinctive immune cells infiltration and suffered an immunosuppressive state. Additionally, this system is closely linked to various classical immunotherapy biomarkers. Conclusion we constructed a novel immune checkpoints-based system for LUAD, which predicts prognosis and immunotherapeutic implications. We believe that these findings will not only aid in clinical management but will also shed some light on screening appropriate patients for immunotherapy. |
| first_indexed | 2024-12-10T21:01:19Z |
| format | Article |
| id | doaj.art-fc18d57105884010b1d93e135a9ee31c |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-10T21:01:19Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-fc18d57105884010b1d93e135a9ee31c2022-12-22T01:33:47ZengBMCJournal of Translational Medicine1479-58762022-07-0120111510.1186/s12967-022-03520-6A novel immune checkpoints-based signature to predict prognosis and response to immunotherapy in lung adenocarcinomaNan Sun0Yuejun Luo1Bo Zheng2Zhihui Zhang3Chaoqi Zhang4Zhen Zhang5Guochao Zhang6Fengwei Tan7Qi Xue8Shugeng Gao9Jie He10Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBiotherapy Center, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeAbstract Background Except for B7-CD28 family members, more novel immune checkpoints are being discovered. They are closely associated with tumor immune microenvironment and regulate the function of many immune cells. Various cancer therapeutic studies targeting these novel immune checkpoints are currently in full swing. However, studies concerning novel immune checkpoints phenotypes and clinical significance in lung adenocarcinoma (LUAD) are still limited. Methods We enrolled 1883 LUAD cases from nine different cohorts. The samples from The Cancer Genome Atlas (TCGA) were used as a training set, whereas seven microarray data cohorts and an independent cohort with 102 qPCR data were used for validation. The immune profiles and potential mechanism of the system were also explored. Results After univariate Cox proportional hazards regression and stepwise multivariable Cox analysis, a novel immune checkpoints-based system (LTA, CD160, and CD40LG) were identified from the training set, which significantly stratified patients into high- and low-risk groups with different survivals. Furthermore, this system has been well validated in different clinical subgroups and multiple validation cohorts. It also acted as an independent prognostic factor for patients with LAUD in different cohorts. Further exploration suggested that high-risk patients exhibited distinctive immune cells infiltration and suffered an immunosuppressive state. Additionally, this system is closely linked to various classical immunotherapy biomarkers. Conclusion we constructed a novel immune checkpoints-based system for LUAD, which predicts prognosis and immunotherapeutic implications. We believe that these findings will not only aid in clinical management but will also shed some light on screening appropriate patients for immunotherapy.https://doi.org/10.1186/s12967-022-03520-6Lung adenocarcinomaImmune checkpointsPrognosisPD-L1Immunotherapy |
| spellingShingle | Nan Sun Yuejun Luo Bo Zheng Zhihui Zhang Chaoqi Zhang Zhen Zhang Guochao Zhang Fengwei Tan Qi Xue Shugeng Gao Jie He A novel immune checkpoints-based signature to predict prognosis and response to immunotherapy in lung adenocarcinoma Journal of Translational Medicine Lung adenocarcinoma Immune checkpoints Prognosis PD-L1 Immunotherapy |
| title | A novel immune checkpoints-based signature to predict prognosis and response to immunotherapy in lung adenocarcinoma |
| title_full | A novel immune checkpoints-based signature to predict prognosis and response to immunotherapy in lung adenocarcinoma |
| title_fullStr | A novel immune checkpoints-based signature to predict prognosis and response to immunotherapy in lung adenocarcinoma |
| title_full_unstemmed | A novel immune checkpoints-based signature to predict prognosis and response to immunotherapy in lung adenocarcinoma |
| title_short | A novel immune checkpoints-based signature to predict prognosis and response to immunotherapy in lung adenocarcinoma |
| title_sort | novel immune checkpoints based signature to predict prognosis and response to immunotherapy in lung adenocarcinoma |
| topic | Lung adenocarcinoma Immune checkpoints Prognosis PD-L1 Immunotherapy |
| url | https://doi.org/10.1186/s12967-022-03520-6 |
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