A tumor mutational burden-derived immune computational framework selects sensitive immunotherapy/chemotherapy for lung adenocarcinoma populations with different prognoses
BackgroundLung adenocarcinoma (LUAD) kills millions of people every year. Recently, FDA and researchers proved the significance of high tumor mutational burden (TMB) in treating solid tumors. But no scholar has constructed a TMB-derived computing framework to select sensitive immunotherapy/chemother...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1104137/full |
| _version_ | 1797790940862087168 |
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| author | Wenlong Zhang Chuzhong Wei Fengyu Huang Wencheng Huang Xiaoxin Xu Xiao Zhu |
| author_facet | Wenlong Zhang Chuzhong Wei Fengyu Huang Wencheng Huang Xiaoxin Xu Xiao Zhu |
| author_sort | Wenlong Zhang |
| collection | DOAJ |
| description | BackgroundLung adenocarcinoma (LUAD) kills millions of people every year. Recently, FDA and researchers proved the significance of high tumor mutational burden (TMB) in treating solid tumors. But no scholar has constructed a TMB-derived computing framework to select sensitive immunotherapy/chemotherapy for the LUAD population with different prognoses.MethodsThe datasets were collected from TCGA, GTEx, and GEO. We constructed the TMB-derived immune lncRNA prognostic index (TILPI) computing framework based on TMB-related genes identified by weighted gene co-expression network analysis (WGCNA), oncogenes, and immune-related genes. Furthermore, we mapped the immune landscape based on eight algorithms. We explored the immunotherapy sensitivity of different prognostic populations based on immunotherapy response, tumor immune dysfunction and exclusion (TIDE), and tumor inflammation signature (TIS) model. Furthermore, the molecular docking models were constructed for sensitive drugs identified by the pRRophetic package, oncopredict package, and connectivity map (CMap).ResultsThe TILPI computing framework was based on the expression of TMB-derived immune lncRNA signature (TILncSig), which consisted of AC091057.1, AC112721.1, AC114763.1, AC129492.1, LINC00592, and TARID. TILPI divided all LUAD patients into two populations with different prognoses. The random grouping verification, survival analysis, 3D PCA, and ROC curve (AUC=0.74) firmly proved the reliability of TILPI. TILPI was associated with clinical characteristics, including smoking and pathological stage. Furthermore, we estimated three types of immune cells threatening the survival of patients based on multiple algorithms. They were macrophage M0, T cell CD4 Th2, and T cell CD4 memory activated. Nevertheless, five immune cells, including B cell, endothelial cell, eosinophil, mast cell, and T cell CD4 memory resting, prolonged the survival. In addition, the immunotherapy response and TIDE model proved the sensitivity of the low-TILPI population to immunotherapy. We also identified seven intersected drugs for the LUAD population with poor prognosis, which included docetaxel, gemcitabine, paclitaxel, palbociclib, pyrimethamine, thapsigargin, and vinorelbine. Their molecular docking models and best binding energy were also constructed and calculated.ConclusionsWe divided all LUAD patients into two populations with different prognoses. The good prognosis population was sensitive to immunotherapy, while the people with poor prognosis benefitted from 7 drugs. |
| first_indexed | 2024-03-13T02:12:40Z |
| format | Article |
| id | doaj.art-106fc34cf21740748dc71d7d9ef1e4a6 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-13T02:12:40Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj.art-106fc34cf21740748dc71d7d9ef1e4a62023-06-30T20:50:26ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-06-011310.3389/fonc.2023.11041371104137A tumor mutational burden-derived immune computational framework selects sensitive immunotherapy/chemotherapy for lung adenocarcinoma populations with different prognosesWenlong Zhang0Chuzhong Wei1Fengyu Huang2Wencheng Huang3Xiaoxin Xu4Xiao Zhu5Huizhou First Hospital, Guangdong Medical University, Huizhou, ChinaHuizhou First Hospital, Guangdong Medical University, Huizhou, ChinaHuizhou First Hospital, Guangdong Medical University, Huizhou, ChinaHuizhou First Hospital, Guangdong Medical University, Huizhou, ChinaHuizhou First Hospital, Guangdong Medical University, Huizhou, ChinaComputational Oncology Laboratory, The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, ChinaBackgroundLung adenocarcinoma (LUAD) kills millions of people every year. Recently, FDA and researchers proved the significance of high tumor mutational burden (TMB) in treating solid tumors. But no scholar has constructed a TMB-derived computing framework to select sensitive immunotherapy/chemotherapy for the LUAD population with different prognoses.MethodsThe datasets were collected from TCGA, GTEx, and GEO. We constructed the TMB-derived immune lncRNA prognostic index (TILPI) computing framework based on TMB-related genes identified by weighted gene co-expression network analysis (WGCNA), oncogenes, and immune-related genes. Furthermore, we mapped the immune landscape based on eight algorithms. We explored the immunotherapy sensitivity of different prognostic populations based on immunotherapy response, tumor immune dysfunction and exclusion (TIDE), and tumor inflammation signature (TIS) model. Furthermore, the molecular docking models were constructed for sensitive drugs identified by the pRRophetic package, oncopredict package, and connectivity map (CMap).ResultsThe TILPI computing framework was based on the expression of TMB-derived immune lncRNA signature (TILncSig), which consisted of AC091057.1, AC112721.1, AC114763.1, AC129492.1, LINC00592, and TARID. TILPI divided all LUAD patients into two populations with different prognoses. The random grouping verification, survival analysis, 3D PCA, and ROC curve (AUC=0.74) firmly proved the reliability of TILPI. TILPI was associated with clinical characteristics, including smoking and pathological stage. Furthermore, we estimated three types of immune cells threatening the survival of patients based on multiple algorithms. They were macrophage M0, T cell CD4 Th2, and T cell CD4 memory activated. Nevertheless, five immune cells, including B cell, endothelial cell, eosinophil, mast cell, and T cell CD4 memory resting, prolonged the survival. In addition, the immunotherapy response and TIDE model proved the sensitivity of the low-TILPI population to immunotherapy. We also identified seven intersected drugs for the LUAD population with poor prognosis, which included docetaxel, gemcitabine, paclitaxel, palbociclib, pyrimethamine, thapsigargin, and vinorelbine. Their molecular docking models and best binding energy were also constructed and calculated.ConclusionsWe divided all LUAD patients into two populations with different prognoses. The good prognosis population was sensitive to immunotherapy, while the people with poor prognosis benefitted from 7 drugs.https://www.frontiersin.org/articles/10.3389/fonc.2023.1104137/fulllung adenocarcinomatumor mutational burdenprediction of prognosisimmune landscapeimmunotherapychemotherapy |
| spellingShingle | Wenlong Zhang Chuzhong Wei Fengyu Huang Wencheng Huang Xiaoxin Xu Xiao Zhu A tumor mutational burden-derived immune computational framework selects sensitive immunotherapy/chemotherapy for lung adenocarcinoma populations with different prognoses Frontiers in Oncology lung adenocarcinoma tumor mutational burden prediction of prognosis immune landscape immunotherapy chemotherapy |
| title | A tumor mutational burden-derived immune computational framework selects sensitive immunotherapy/chemotherapy for lung adenocarcinoma populations with different prognoses |
| title_full | A tumor mutational burden-derived immune computational framework selects sensitive immunotherapy/chemotherapy for lung adenocarcinoma populations with different prognoses |
| title_fullStr | A tumor mutational burden-derived immune computational framework selects sensitive immunotherapy/chemotherapy for lung adenocarcinoma populations with different prognoses |
| title_full_unstemmed | A tumor mutational burden-derived immune computational framework selects sensitive immunotherapy/chemotherapy for lung adenocarcinoma populations with different prognoses |
| title_short | A tumor mutational burden-derived immune computational framework selects sensitive immunotherapy/chemotherapy for lung adenocarcinoma populations with different prognoses |
| title_sort | tumor mutational burden derived immune computational framework selects sensitive immunotherapy chemotherapy for lung adenocarcinoma populations with different prognoses |
| topic | lung adenocarcinoma tumor mutational burden prediction of prognosis immune landscape immunotherapy chemotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1104137/full |
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