Advances in lung adenocarcinoma: A novel perspective on prognoses and immune responses of CENPO as an oncogenic superenhancer
Lung adenocarcinoma (LUAD) is the most prevalent form of lung cancer globally, and its treatment remains a significant challenge. Therefore, it is crucial to comprehend the microenvironment to improve therapy and prognosis urgently. In this study, we utilized bioinformatic methods to analyze the tra...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-08-01
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| Series: | Translational Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523323000773 |
| _version_ | 1797802884489805824 |
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| author | Tongdong Shi Zaoxiu Hu Li Tian Yanlong Yang |
| author_facet | Tongdong Shi Zaoxiu Hu Li Tian Yanlong Yang |
| author_sort | Tongdong Shi |
| collection | DOAJ |
| description | Lung adenocarcinoma (LUAD) is the most prevalent form of lung cancer globally, and its treatment remains a significant challenge. Therefore, it is crucial to comprehend the microenvironment to improve therapy and prognosis urgently. In this study, we utilized bioinformatic methods to analyze the transcription expression profile of patient samples with complete clinical information from the TCGA-LUAD datasets. To validate our findings, we also analyzed the Gene Expression Omnibus (GEO) datasets. The super-enhancer (SE) was visualized using the peaks of the H3K27ac and H3K4me1 ChIP-seq signal, which were identified by the Integrative Genomics Viewer (IGV). To further investigate the role of Centromere protein O (CENPO) in LUAD, we conducted various assays including Western blot, qRT-PCR, flow cytometry, wound healing and transwell assays to assess the cell functions of CENPO in vitro. The overexpression of CENPO is linked to a poor prognosis in patients with LUAD. Strong signal peaks of H3K27ac and H3K4me1 were also observed near the predicted SE regions of CENPO. CENPO was found to be positively associated with the expression levels of immune checkpoints and drug IC50 value (Roscovitine and TGX221), but negatively associated with the fraction levels of several immature cells and drug IC50 value (CCT018159, GSK1904529A, Lenaildomide, and PD-173074). Additionally, CENPO-associated prognostic signature (CPS) was identified as an independent risk factor. The high-risk group for LUAD is identified based on CPS enrichment, which involved not only endocytosis that transfers mitochondria to promote cell survival in response to chemotherapy but also cell cycle promotion that leads to drug resistance. The removal of CENPO significantly suppressed metastasis and induced arrest and apoptosis of LUAD cells. The involvement of CENPO in the immunosuppression of LUAD provides a prognostic signature for LUAD patients. |
| first_indexed | 2024-03-13T05:12:29Z |
| format | Article |
| id | doaj.art-e26e7824fc6a4d558efcd3bd21c719c5 |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-03-13T05:12:29Z |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-e26e7824fc6a4d558efcd3bd21c719c52023-06-16T05:09:16ZengElsevierTranslational Oncology1936-52332023-08-0134101691Advances in lung adenocarcinoma: A novel perspective on prognoses and immune responses of CENPO as an oncogenic superenhancerTongdong Shi0Zaoxiu Hu1Li Tian2Yanlong Yang3Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), The Second Affiliated Hospital of Chongqing Medical University, No.288 Tianwen Avenue, Nan'an District, Chongqing 401336, People's Republic of ChinaDepartment of Pathology, The Third Affiliated Hospital of Kunming Medical University, No.519 Kunzhou Road, Xishan District, Kunming, Yunnan 650118, People's Republic of ChinaDepartment of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), The Second Affiliated Hospital of Chongqing Medical University, No.288 Tianwen Avenue, Nan'an District, Chongqing 401336, People's Republic of ChinaDepartment of Thoracic Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, People's Republic of China; Corresponding author.Lung adenocarcinoma (LUAD) is the most prevalent form of lung cancer globally, and its treatment remains a significant challenge. Therefore, it is crucial to comprehend the microenvironment to improve therapy and prognosis urgently. In this study, we utilized bioinformatic methods to analyze the transcription expression profile of patient samples with complete clinical information from the TCGA-LUAD datasets. To validate our findings, we also analyzed the Gene Expression Omnibus (GEO) datasets. The super-enhancer (SE) was visualized using the peaks of the H3K27ac and H3K4me1 ChIP-seq signal, which were identified by the Integrative Genomics Viewer (IGV). To further investigate the role of Centromere protein O (CENPO) in LUAD, we conducted various assays including Western blot, qRT-PCR, flow cytometry, wound healing and transwell assays to assess the cell functions of CENPO in vitro. The overexpression of CENPO is linked to a poor prognosis in patients with LUAD. Strong signal peaks of H3K27ac and H3K4me1 were also observed near the predicted SE regions of CENPO. CENPO was found to be positively associated with the expression levels of immune checkpoints and drug IC50 value (Roscovitine and TGX221), but negatively associated with the fraction levels of several immature cells and drug IC50 value (CCT018159, GSK1904529A, Lenaildomide, and PD-173074). Additionally, CENPO-associated prognostic signature (CPS) was identified as an independent risk factor. The high-risk group for LUAD is identified based on CPS enrichment, which involved not only endocytosis that transfers mitochondria to promote cell survival in response to chemotherapy but also cell cycle promotion that leads to drug resistance. The removal of CENPO significantly suppressed metastasis and induced arrest and apoptosis of LUAD cells. The involvement of CENPO in the immunosuppression of LUAD provides a prognostic signature for LUAD patients.http://www.sciencedirect.com/science/article/pii/S1936523323000773Lung adenocarcinomaCENPOCell cycleImmuneCENPO-associated prognostic signature (CPS) |
| spellingShingle | Tongdong Shi Zaoxiu Hu Li Tian Yanlong Yang Advances in lung adenocarcinoma: A novel perspective on prognoses and immune responses of CENPO as an oncogenic superenhancer Translational Oncology Lung adenocarcinoma CENPO Cell cycle Immune CENPO-associated prognostic signature (CPS) |
| title | Advances in lung adenocarcinoma: A novel perspective on prognoses and immune responses of CENPO as an oncogenic superenhancer |
| title_full | Advances in lung adenocarcinoma: A novel perspective on prognoses and immune responses of CENPO as an oncogenic superenhancer |
| title_fullStr | Advances in lung adenocarcinoma: A novel perspective on prognoses and immune responses of CENPO as an oncogenic superenhancer |
| title_full_unstemmed | Advances in lung adenocarcinoma: A novel perspective on prognoses and immune responses of CENPO as an oncogenic superenhancer |
| title_short | Advances in lung adenocarcinoma: A novel perspective on prognoses and immune responses of CENPO as an oncogenic superenhancer |
| title_sort | advances in lung adenocarcinoma a novel perspective on prognoses and immune responses of cenpo as an oncogenic superenhancer |
| topic | Lung adenocarcinoma CENPO Cell cycle Immune CENPO-associated prognostic signature (CPS) |
| url | http://www.sciencedirect.com/science/article/pii/S1936523323000773 |
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