Combining single-cell analysis and molecular docking techniques to construct a prognostic model for colon adenocarcinoma and uncovering inhibin subunit βb as a novel therapeutic target
BackgroundColon adenocarcinoma (COAD) is a malignancy with a high mortality rate and complex biological characteristics and heterogeneity, which poses challenges for clinical treatment. Anoikis is a type of programmed cell death that occurs when cells lose their attachment to the extracellular matri...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1524560/full |
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| author | Qinqing Wu Qinqing Wu Lu Ye Yuwei Wu Mengyu Zhao Mengyu Zhao Jiaxin Lu Yanping Yu Yanping Yu Yixiao Niu Yixiao Niu Luxiao Zhang Peijun Zuo Peijun Zuo |
| author_facet | Qinqing Wu Qinqing Wu Lu Ye Yuwei Wu Mengyu Zhao Mengyu Zhao Jiaxin Lu Yanping Yu Yanping Yu Yixiao Niu Yixiao Niu Luxiao Zhang Peijun Zuo Peijun Zuo |
| author_sort | Qinqing Wu |
| collection | DOAJ |
| description | BackgroundColon adenocarcinoma (COAD) is a malignancy with a high mortality rate and complex biological characteristics and heterogeneity, which poses challenges for clinical treatment. Anoikis is a type of programmed cell death that occurs when cells lose their attachment to the extracellular matrix (ECM), and it plays a crucial role in tumor metastasis. However, the specific biological link between anoikis and COAD, as well as its mechanisms in tumor progression, remains unclear, making it a potential new direction for therapeutic strategy research.MethodsWe employed transcriptomic data and clinical information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to pinpoint differentially expressed anoikis-related genes (ARGs) in COAD. Using Cox proportional hazards models and Lasso regression analysis, we developed a prognostic signature derived from these ARGs. We also investigated the roles and interactions of these genes in the tumor microenvironment by analyzing single-cell RNA sequencing data. Additionally, we employed molecular docking techniques to evaluate the potential of inhibin subunit beta B (INHBB) as therapeutic targets and to assess the binding affinity of candidate drugs. Finally, we used gene knockout techniques to silence the key gene INHBB and explored its biological functions in vitro.ResultsIn our study, by analyzing the expression differences of ARGs, we successfully classified patients with COAD. Kaplan-Meier survival analysis demonstrated that patients with elevated risk scores experienced poorer prognosis, a finding that was confirmed in both the training and validation cohorts. Additionally, immune infiltration analysis revealed a notable increase in immune cell presence within the tumor microenvironment of high-risk patients. Molecular docking identified potential drug candidates with high binding affinity to INHBB, including risperidone. Furthermore, in vitro experiments with INHBB showed that downregulation of its expression in COAD cell lines significantly reduced cellular viability and migration capacity.ConclusionIn summary, our research, based on the expression characteristics of ARGs, provides new insights into the precise classification, prognosis assessment, and identification of potential therapeutic targets in COAD. It also validates the key role of INHBB in the progression of COAD, establishing the foundation for future personalized treatment strategies. |
| format | Article |
| id | doaj-art-64e3fbceae7e44a1b5b5403b13a2176c |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-64e3fbceae7e44a1b5b5403b13a2176c2025-01-09T06:10:40ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.15245601524560Combining single-cell analysis and molecular docking techniques to construct a prognostic model for colon adenocarcinoma and uncovering inhibin subunit βb as a novel therapeutic targetQinqing Wu0Qinqing Wu1Lu Ye2Yuwei Wu3Mengyu Zhao4Mengyu Zhao5Jiaxin Lu6Yanping Yu7Yanping Yu8Yixiao Niu9Yixiao Niu10Luxiao Zhang11Peijun Zuo12Peijun Zuo13Department of Preventive Medicine, Shantou University Medical College, Shantou, ChinaSchool of Public Health, Shantou University, Shantou, ChinaDepartment of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of General Surgery, Union Hospital affiliated to Fujian Medical University, Fuzhou, ChinaDepartment of Preventive Medicine, Shantou University Medical College, Shantou, ChinaDepartment of Neurosurgery, First Affiliated Hospital of Anhui Medical University, Hefei, ChinaDepartment of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Preventive Medicine, Shantou University Medical College, Shantou, ChinaSchool of Public Health, Shantou University, Shantou, ChinaDepartment of Preventive Medicine, Shantou University Medical College, Shantou, ChinaSchool of Public Health, Shantou University, Shantou, ChinaDepartment of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Preventive Medicine, Shantou University Medical College, Shantou, ChinaSchool of Public Health, Shantou University, Shantou, ChinaBackgroundColon adenocarcinoma (COAD) is a malignancy with a high mortality rate and complex biological characteristics and heterogeneity, which poses challenges for clinical treatment. Anoikis is a type of programmed cell death that occurs when cells lose their attachment to the extracellular matrix (ECM), and it plays a crucial role in tumor metastasis. However, the specific biological link between anoikis and COAD, as well as its mechanisms in tumor progression, remains unclear, making it a potential new direction for therapeutic strategy research.MethodsWe employed transcriptomic data and clinical information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to pinpoint differentially expressed anoikis-related genes (ARGs) in COAD. Using Cox proportional hazards models and Lasso regression analysis, we developed a prognostic signature derived from these ARGs. We also investigated the roles and interactions of these genes in the tumor microenvironment by analyzing single-cell RNA sequencing data. Additionally, we employed molecular docking techniques to evaluate the potential of inhibin subunit beta B (INHBB) as therapeutic targets and to assess the binding affinity of candidate drugs. Finally, we used gene knockout techniques to silence the key gene INHBB and explored its biological functions in vitro.ResultsIn our study, by analyzing the expression differences of ARGs, we successfully classified patients with COAD. Kaplan-Meier survival analysis demonstrated that patients with elevated risk scores experienced poorer prognosis, a finding that was confirmed in both the training and validation cohorts. Additionally, immune infiltration analysis revealed a notable increase in immune cell presence within the tumor microenvironment of high-risk patients. Molecular docking identified potential drug candidates with high binding affinity to INHBB, including risperidone. Furthermore, in vitro experiments with INHBB showed that downregulation of its expression in COAD cell lines significantly reduced cellular viability and migration capacity.ConclusionIn summary, our research, based on the expression characteristics of ARGs, provides new insights into the precise classification, prognosis assessment, and identification of potential therapeutic targets in COAD. It also validates the key role of INHBB in the progression of COAD, establishing the foundation for future personalized treatment strategies.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1524560/fullanoikiscolon adenocarcinomasingle-cell analysismolecular dockingINHBB 1 |
| spellingShingle | Qinqing Wu Qinqing Wu Lu Ye Yuwei Wu Mengyu Zhao Mengyu Zhao Jiaxin Lu Yanping Yu Yanping Yu Yixiao Niu Yixiao Niu Luxiao Zhang Peijun Zuo Peijun Zuo Combining single-cell analysis and molecular docking techniques to construct a prognostic model for colon adenocarcinoma and uncovering inhibin subunit βb as a novel therapeutic target Frontiers in Immunology anoikis colon adenocarcinoma single-cell analysis molecular docking INHBB 1 |
| title | Combining single-cell analysis and molecular docking techniques to construct a prognostic model for colon adenocarcinoma and uncovering inhibin subunit βb as a novel therapeutic target |
| title_full | Combining single-cell analysis and molecular docking techniques to construct a prognostic model for colon adenocarcinoma and uncovering inhibin subunit βb as a novel therapeutic target |
| title_fullStr | Combining single-cell analysis and molecular docking techniques to construct a prognostic model for colon adenocarcinoma and uncovering inhibin subunit βb as a novel therapeutic target |
| title_full_unstemmed | Combining single-cell analysis and molecular docking techniques to construct a prognostic model for colon adenocarcinoma and uncovering inhibin subunit βb as a novel therapeutic target |
| title_short | Combining single-cell analysis and molecular docking techniques to construct a prognostic model for colon adenocarcinoma and uncovering inhibin subunit βb as a novel therapeutic target |
| title_sort | combining single cell analysis and molecular docking techniques to construct a prognostic model for colon adenocarcinoma and uncovering inhibin subunit βb as a novel therapeutic target |
| topic | anoikis colon adenocarcinoma single-cell analysis molecular docking INHBB 1 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1524560/full |
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