Characterization of the Oncogenic Potential of Eukaryotic Initiation Factor 4A1 in Lung Adenocarcinoma via Cell Cycle Regulation and Immune Microenvironment Reprogramming
Lung adenocarcinoma (LUAD) is a common type of lung cancer. Although the diagnosis and treatment of LUAD have significantly improved in recent decades, the survival for advanced LUAD is still poor. It is necessary to identify more targets for developing potential agents against LUAD. This study expl...
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2022-06-01
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| author | Kuan-Li Wu Yung-Chi Huang Yu-Yuan Wu Chao-Yuan Chang Yung-Yun Chang Hung-Hsing Chiang Lian-Xiu Liu Ying-Ming Tsai Jen-Yu Hung |
| author_facet | Kuan-Li Wu Yung-Chi Huang Yu-Yuan Wu Chao-Yuan Chang Yung-Yun Chang Hung-Hsing Chiang Lian-Xiu Liu Ying-Ming Tsai Jen-Yu Hung |
| author_sort | Kuan-Li Wu |
| collection | DOAJ |
| description | Lung adenocarcinoma (LUAD) is a common type of lung cancer. Although the diagnosis and treatment of LUAD have significantly improved in recent decades, the survival for advanced LUAD is still poor. It is necessary to identify more targets for developing potential agents against LUAD. This study explored the dysregulation of translation initiation factors, specifically eukaryotic initiation factors 4A1 (<i>EIF4A1</i>) and <i>EIF4A2</i>, in developing LUAD, as well as their underlying mechanisms. We found that the expression of <i>EIF4A1</i>, but not <i>EIF4A2</i>, was higher in tumor tissue and associated with poor clinical outcomes in LUAD patients. Elevated expression of EIF4H with poor prognosis may potentiate the oncogenic role of <i>EIF4A1</i>. Functional enrichment analysis revealed that upregulation of <i>EIF4A1</i> was related to cell cycle regulation and DNA repair. The oncogenic effect of <i>EIF4A1</i> was further elucidated by Gene Set Variation Analysis (GSVA). The GSVA score of the gene set positively correlated with <i>EIF4A1</i> was higher in tumors and significantly associated with worse survival. In the meantime, gene set enrichment analysis (GSEA) also indicated that elevated <i>EIF4A1</i> expression in LUAD patients was associated with a decreased infiltration score for immune cells by reducing anticancer immune cell types and recruiting immunosuppressive cells. Consistent with the results, the GSVA score of genes whose expression was negatively correlated with <i>EIF4A1</i> was lower in the tumor tissue of LUAD cases with worse clinical outcomes and was strongly associated with the disequilibrium of anti-cancer immunity by recruiting anticancer immune cells. Based on the results from the present study, we hypothesize that the dysregulation of <i>EIF4A1</i> might be involved in the pathophysiology of LUAD development by promoting cancer growth and changing the tumor immune microenvironment. This can be used to develop potential diagnostic biomarkers or therapeutic targets for LUAD. |
| first_indexed | 2024-03-09T10:22:15Z |
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| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-09T10:22:15Z |
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| spelling | doaj.art-6a85db564cdf455eab6f3cec9d9cea982023-12-01T21:54:17ZengMDPI AGBiology2079-77372022-06-0111797510.3390/biology11070975Characterization of the Oncogenic Potential of Eukaryotic Initiation Factor 4A1 in Lung Adenocarcinoma via Cell Cycle Regulation and Immune Microenvironment ReprogrammingKuan-Li Wu0Yung-Chi Huang1Yu-Yuan Wu2Chao-Yuan Chang3Yung-Yun Chang4Hung-Hsing Chiang5Lian-Xiu Liu6Ying-Ming Tsai7Jen-Yu Hung8Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanSchool of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanDivision of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, TaiwanDivision of Thoracic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanDivision of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, TaiwanDivision of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, TaiwanLung adenocarcinoma (LUAD) is a common type of lung cancer. Although the diagnosis and treatment of LUAD have significantly improved in recent decades, the survival for advanced LUAD is still poor. It is necessary to identify more targets for developing potential agents against LUAD. This study explored the dysregulation of translation initiation factors, specifically eukaryotic initiation factors 4A1 (<i>EIF4A1</i>) and <i>EIF4A2</i>, in developing LUAD, as well as their underlying mechanisms. We found that the expression of <i>EIF4A1</i>, but not <i>EIF4A2</i>, was higher in tumor tissue and associated with poor clinical outcomes in LUAD patients. Elevated expression of EIF4H with poor prognosis may potentiate the oncogenic role of <i>EIF4A1</i>. Functional enrichment analysis revealed that upregulation of <i>EIF4A1</i> was related to cell cycle regulation and DNA repair. The oncogenic effect of <i>EIF4A1</i> was further elucidated by Gene Set Variation Analysis (GSVA). The GSVA score of the gene set positively correlated with <i>EIF4A1</i> was higher in tumors and significantly associated with worse survival. In the meantime, gene set enrichment analysis (GSEA) also indicated that elevated <i>EIF4A1</i> expression in LUAD patients was associated with a decreased infiltration score for immune cells by reducing anticancer immune cell types and recruiting immunosuppressive cells. Consistent with the results, the GSVA score of genes whose expression was negatively correlated with <i>EIF4A1</i> was lower in the tumor tissue of LUAD cases with worse clinical outcomes and was strongly associated with the disequilibrium of anti-cancer immunity by recruiting anticancer immune cells. Based on the results from the present study, we hypothesize that the dysregulation of <i>EIF4A1</i> might be involved in the pathophysiology of LUAD development by promoting cancer growth and changing the tumor immune microenvironment. This can be used to develop potential diagnostic biomarkers or therapeutic targets for LUAD.https://www.mdpi.com/2079-7737/11/7/975cell cycleDNA repair<i>EIF4A1</i>LUADtumor immune microenvironment |
| spellingShingle | Kuan-Li Wu Yung-Chi Huang Yu-Yuan Wu Chao-Yuan Chang Yung-Yun Chang Hung-Hsing Chiang Lian-Xiu Liu Ying-Ming Tsai Jen-Yu Hung Characterization of the Oncogenic Potential of Eukaryotic Initiation Factor 4A1 in Lung Adenocarcinoma via Cell Cycle Regulation and Immune Microenvironment Reprogramming Biology cell cycle DNA repair <i>EIF4A1</i> LUAD tumor immune microenvironment |
| title | Characterization of the Oncogenic Potential of Eukaryotic Initiation Factor 4A1 in Lung Adenocarcinoma via Cell Cycle Regulation and Immune Microenvironment Reprogramming |
| title_full | Characterization of the Oncogenic Potential of Eukaryotic Initiation Factor 4A1 in Lung Adenocarcinoma via Cell Cycle Regulation and Immune Microenvironment Reprogramming |
| title_fullStr | Characterization of the Oncogenic Potential of Eukaryotic Initiation Factor 4A1 in Lung Adenocarcinoma via Cell Cycle Regulation and Immune Microenvironment Reprogramming |
| title_full_unstemmed | Characterization of the Oncogenic Potential of Eukaryotic Initiation Factor 4A1 in Lung Adenocarcinoma via Cell Cycle Regulation and Immune Microenvironment Reprogramming |
| title_short | Characterization of the Oncogenic Potential of Eukaryotic Initiation Factor 4A1 in Lung Adenocarcinoma via Cell Cycle Regulation and Immune Microenvironment Reprogramming |
| title_sort | characterization of the oncogenic potential of eukaryotic initiation factor 4a1 in lung adenocarcinoma via cell cycle regulation and immune microenvironment reprogramming |
| topic | cell cycle DNA repair <i>EIF4A1</i> LUAD tumor immune microenvironment |
| url | https://www.mdpi.com/2079-7737/11/7/975 |
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