Integrative analysis and experiments to explore angiogenesis regulators correlated with poor prognosis, immune infiltration and cancer progression in lung adenocarcinoma
Abstract Angiogenesis is the process of capillary sprouting from pre-existing vessels and it plays a critical role in the carcinogenic process of lung adenocarcinoma (LUAD). However, the association of angiogenesis regulators with the prognosis and progression of LUAD needs to be further elucidated....
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-08-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-021-03031-w |
| _version_ | 1818722077097590784 |
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| author | Songhua Cai Xiaotong Guo Chujian Huang Youjun Deng Longde Du Wenyi Liu Chenglin Yang Hongbo Zhao Kai Ma Lixu Wang Jie He Zhentao Yu |
| author_facet | Songhua Cai Xiaotong Guo Chujian Huang Youjun Deng Longde Du Wenyi Liu Chenglin Yang Hongbo Zhao Kai Ma Lixu Wang Jie He Zhentao Yu |
| author_sort | Songhua Cai |
| collection | DOAJ |
| description | Abstract Angiogenesis is the process of capillary sprouting from pre-existing vessels and it plays a critical role in the carcinogenic process of lung adenocarcinoma (LUAD). However, the association of angiogenesis regulators with the prognosis and progression of LUAD needs to be further elucidated. In this study, we adopted differential expression analysis, Cox proportional hazards (PH) regression analysis and experimental validation to identify angiogenesis regulators correlated with a poor prognosis, immune infiltration and cancer progression in LUAD. These results showed that the diagnostic and prognostic models based on COL5A2 and EPHB2 served as independent biomarkers with superior predictive ability. The patients in the high-risk group exhibited a worse prognosis in the TCGA cohort (P < 0.001, HR = 1.72, 95% CI 1.28–2.30), GSE310210 cohort (P = 0.005, HR = 2.87, 95% CI 1.46–5.61), and GSE31019 cohort (P = 0.01, HR = 2.14, 95% CI 1.19–3.86) than patients in the low-risk group. The high prognostic risk patients had a higher TMB (P < 0.001); higher fractions of M0 macrophages, neutrophils, NK cells resting, and T cells CD4 memory activated (P < 0.05); and higher expression of immune checkpoints PD-1, PDL-1, PDL-2, and B7H3 (P < 0.001). Patients in the high-risk group were more sensitive to chemotherapeutic drugs and molecular targeted drugs such as cisplatin, doxorubicin, gefitinib, and bosutinib (P < 0.0001). In addition, inhibition of COL5A2 and EPHB2 effectively suppressed the proliferation and migration of LUAD cells. The current study identified angiogenesis regulators as potential biomarkers and therapeutic targets for LUAD and may help to further optimize cancer therapy. |
| first_indexed | 2024-12-17T20:48:53Z |
| format | Article |
| id | doaj.art-de273da9b1f647e49ad6365f8aef5155 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-17T20:48:53Z |
| publishDate | 2021-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-de273da9b1f647e49ad6365f8aef51552022-12-21T21:33:06ZengBMCJournal of Translational Medicine1479-58762021-08-0119111610.1186/s12967-021-03031-wIntegrative analysis and experiments to explore angiogenesis regulators correlated with poor prognosis, immune infiltration and cancer progression in lung adenocarcinomaSonghua Cai0Xiaotong Guo1Chujian Huang2Youjun Deng3Longde Du4Wenyi Liu5Chenglin Yang6Hongbo Zhao7Kai Ma8Lixu Wang9Jie He10Zhentao Yu11Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen 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 & Shenzhen 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 & Shenzhen 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 & Shenzhen 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 & Shenzhen 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 & Shenzhen 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 & Shenzhen 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 & Shenzhen 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 & Shenzhen 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 & Shenzhen 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 & Shenzhen 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 & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeAbstract Angiogenesis is the process of capillary sprouting from pre-existing vessels and it plays a critical role in the carcinogenic process of lung adenocarcinoma (LUAD). However, the association of angiogenesis regulators with the prognosis and progression of LUAD needs to be further elucidated. In this study, we adopted differential expression analysis, Cox proportional hazards (PH) regression analysis and experimental validation to identify angiogenesis regulators correlated with a poor prognosis, immune infiltration and cancer progression in LUAD. These results showed that the diagnostic and prognostic models based on COL5A2 and EPHB2 served as independent biomarkers with superior predictive ability. The patients in the high-risk group exhibited a worse prognosis in the TCGA cohort (P < 0.001, HR = 1.72, 95% CI 1.28–2.30), GSE310210 cohort (P = 0.005, HR = 2.87, 95% CI 1.46–5.61), and GSE31019 cohort (P = 0.01, HR = 2.14, 95% CI 1.19–3.86) than patients in the low-risk group. The high prognostic risk patients had a higher TMB (P < 0.001); higher fractions of M0 macrophages, neutrophils, NK cells resting, and T cells CD4 memory activated (P < 0.05); and higher expression of immune checkpoints PD-1, PDL-1, PDL-2, and B7H3 (P < 0.001). Patients in the high-risk group were more sensitive to chemotherapeutic drugs and molecular targeted drugs such as cisplatin, doxorubicin, gefitinib, and bosutinib (P < 0.0001). In addition, inhibition of COL5A2 and EPHB2 effectively suppressed the proliferation and migration of LUAD cells. The current study identified angiogenesis regulators as potential biomarkers and therapeutic targets for LUAD and may help to further optimize cancer therapy.https://doi.org/10.1186/s12967-021-03031-wAngiogenesisLUADImmune checkpointChemotherapy |
| spellingShingle | Songhua Cai Xiaotong Guo Chujian Huang Youjun Deng Longde Du Wenyi Liu Chenglin Yang Hongbo Zhao Kai Ma Lixu Wang Jie He Zhentao Yu Integrative analysis and experiments to explore angiogenesis regulators correlated with poor prognosis, immune infiltration and cancer progression in lung adenocarcinoma Journal of Translational Medicine Angiogenesis LUAD Immune checkpoint Chemotherapy |
| title | Integrative analysis and experiments to explore angiogenesis regulators correlated with poor prognosis, immune infiltration and cancer progression in lung adenocarcinoma |
| title_full | Integrative analysis and experiments to explore angiogenesis regulators correlated with poor prognosis, immune infiltration and cancer progression in lung adenocarcinoma |
| title_fullStr | Integrative analysis and experiments to explore angiogenesis regulators correlated with poor prognosis, immune infiltration and cancer progression in lung adenocarcinoma |
| title_full_unstemmed | Integrative analysis and experiments to explore angiogenesis regulators correlated with poor prognosis, immune infiltration and cancer progression in lung adenocarcinoma |
| title_short | Integrative analysis and experiments to explore angiogenesis regulators correlated with poor prognosis, immune infiltration and cancer progression in lung adenocarcinoma |
| title_sort | integrative analysis and experiments to explore angiogenesis regulators correlated with poor prognosis immune infiltration and cancer progression in lung adenocarcinoma |
| topic | Angiogenesis LUAD Immune checkpoint Chemotherapy |
| url | https://doi.org/10.1186/s12967-021-03031-w |
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