An ICD-Associated DAMP Gene signature predicts survival and immunotherapy response of patients with lung adenocarcinoma
Abstract Background While some lung adenocarcinoma (LUAD) patients benefit long-term from treatment with immune checkpoint inhibitors, the sad reality is that a considerable proportion of patients do not. The classification of the LUAD tumor microenvironment (TME) can be used to conceptually compreh...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-05-01
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| Series: | Respiratory Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12931-023-02443-0 |
| _version_ | 1797811371745738752 |
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| author | Yuxin Wu Kexin Li Shuang Liang Xiaoying Lou Yiling Li Danfei Xu Yue Wu Yuan Wang Wei Cui |
| author_facet | Yuxin Wu Kexin Li Shuang Liang Xiaoying Lou Yiling Li Danfei Xu Yue Wu Yuan Wang Wei Cui |
| author_sort | Yuxin Wu |
| collection | DOAJ |
| description | Abstract Background While some lung adenocarcinoma (LUAD) patients benefit long-term from treatment with immune checkpoint inhibitors, the sad reality is that a considerable proportion of patients do not. The classification of the LUAD tumor microenvironment (TME) can be used to conceptually comprehend primary resistance mechanisms. In addition, the most recent research demonstrates that the release of damage-associated molecular pattern (DAMP) in TME by immunogenic cell death (ICD) may contribute to the adaptive immune response. Currently, however, there is no such comprehensive research on this topic in LUAD patients. Therefore, we set out to investigate how to reverse the poor infiltration characteristics of immune cells and boost antitumor immunity by identifying DAMP model. Methods In this study, ICD-related DAMP genes were selected to investigate their effects on the prognosis of LUAD. To create a risk signature using the TCGA-LUAD cohort, the univariate COX regression and the least absolute shrinkage and selection operator regression were carried out, and the results were verified in a GEO dataset. Subsequently, the multivariate COX regression was applied to establish a prognostic nomogram. And the ESTIMATE and ssGSEA algorithms were utilized to analyze immune activity and the TIDE algorithm was for responsiveness to immunotherapy. Moreover, clinical tissue samples were used to verify the differential expression of 9 DAMP genes in the signature. Results We identified two distinct DAMP molecular subtypes, and there are remarkable differences in survival probability between the two subtypes, and patients with higher levels of DAMP-related genes are “hot tumors” with increased immune activity. In addition, 9 DAMP genes were selected as prognostic signature genes, and clinical outcomes and immunotherapy response were better for participants in the low-risk group. Importantly, according to the area under the curve (AUC) value in evaluating the efficacy of immunotherapy, this signature is superior to existing predictors, such as PD-L1 and TIDE. Conclusions Our study suggests ICD plays an important part in modeling the TME of LUAD patients. And this signature could be utilized as a reliable predictor to estimate clinical outcomes and predict immunotherapy efficacy among LUAD patients. |
| first_indexed | 2024-03-13T07:21:40Z |
| format | Article |
| id | doaj.art-e00b3a2c09024cf4ac557494d8c155f3 |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-03-13T07:21:40Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-e00b3a2c09024cf4ac557494d8c155f32023-06-04T11:36:45ZengBMCRespiratory Research1465-993X2023-05-0124111610.1186/s12931-023-02443-0An ICD-Associated DAMP Gene signature predicts survival and immunotherapy response of patients with lung adenocarcinomaYuxin Wu0Kexin Li1Shuang Liang2Xiaoying Lou3Yiling Li4Danfei Xu5Yue Wu6Yuan Wang7Wei Cui8State Key Laboratory of Molecular Oncology, Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeState Key Laboratory of Molecular Oncology, Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeState Key Laboratory of Molecular Oncology, Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeState Key Laboratory of Molecular Oncology, Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeState Key Laboratory of Molecular Oncology, Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeState Key Laboratory of Molecular Oncology, Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeState Key Laboratory of Molecular Oncology, Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeState Key Laboratory of Molecular Oncology, Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeState Key Laboratory of Molecular Oncology, Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeAbstract Background While some lung adenocarcinoma (LUAD) patients benefit long-term from treatment with immune checkpoint inhibitors, the sad reality is that a considerable proportion of patients do not. The classification of the LUAD tumor microenvironment (TME) can be used to conceptually comprehend primary resistance mechanisms. In addition, the most recent research demonstrates that the release of damage-associated molecular pattern (DAMP) in TME by immunogenic cell death (ICD) may contribute to the adaptive immune response. Currently, however, there is no such comprehensive research on this topic in LUAD patients. Therefore, we set out to investigate how to reverse the poor infiltration characteristics of immune cells and boost antitumor immunity by identifying DAMP model. Methods In this study, ICD-related DAMP genes were selected to investigate their effects on the prognosis of LUAD. To create a risk signature using the TCGA-LUAD cohort, the univariate COX regression and the least absolute shrinkage and selection operator regression were carried out, and the results were verified in a GEO dataset. Subsequently, the multivariate COX regression was applied to establish a prognostic nomogram. And the ESTIMATE and ssGSEA algorithms were utilized to analyze immune activity and the TIDE algorithm was for responsiveness to immunotherapy. Moreover, clinical tissue samples were used to verify the differential expression of 9 DAMP genes in the signature. Results We identified two distinct DAMP molecular subtypes, and there are remarkable differences in survival probability between the two subtypes, and patients with higher levels of DAMP-related genes are “hot tumors” with increased immune activity. In addition, 9 DAMP genes were selected as prognostic signature genes, and clinical outcomes and immunotherapy response were better for participants in the low-risk group. Importantly, according to the area under the curve (AUC) value in evaluating the efficacy of immunotherapy, this signature is superior to existing predictors, such as PD-L1 and TIDE. Conclusions Our study suggests ICD plays an important part in modeling the TME of LUAD patients. And this signature could be utilized as a reliable predictor to estimate clinical outcomes and predict immunotherapy efficacy among LUAD patients.https://doi.org/10.1186/s12931-023-02443-0Lung adenocarcinomaImmunogenic cell deathDamage-associated molecular patternsSignaturePrognosisImmunotherapy |
| spellingShingle | Yuxin Wu Kexin Li Shuang Liang Xiaoying Lou Yiling Li Danfei Xu Yue Wu Yuan Wang Wei Cui An ICD-Associated DAMP Gene signature predicts survival and immunotherapy response of patients with lung adenocarcinoma Respiratory Research Lung adenocarcinoma Immunogenic cell death Damage-associated molecular patterns Signature Prognosis Immunotherapy |
| title | An ICD-Associated DAMP Gene signature predicts survival and immunotherapy response of patients with lung adenocarcinoma |
| title_full | An ICD-Associated DAMP Gene signature predicts survival and immunotherapy response of patients with lung adenocarcinoma |
| title_fullStr | An ICD-Associated DAMP Gene signature predicts survival and immunotherapy response of patients with lung adenocarcinoma |
| title_full_unstemmed | An ICD-Associated DAMP Gene signature predicts survival and immunotherapy response of patients with lung adenocarcinoma |
| title_short | An ICD-Associated DAMP Gene signature predicts survival and immunotherapy response of patients with lung adenocarcinoma |
| title_sort | icd associated damp gene signature predicts survival and immunotherapy response of patients with lung adenocarcinoma |
| topic | Lung adenocarcinoma Immunogenic cell death Damage-associated molecular patterns Signature Prognosis Immunotherapy |
| url | https://doi.org/10.1186/s12931-023-02443-0 |
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