Pan-cancer analysis of the immunological and oncogenic roles of ATAD2 with verification in papillary thyroid carcinoma
Abstract ATAD2 (ATPase Family AAA Domain-Containing 2) is highly expressed across varies tumor types, yet its common roles in tumor progression and immune interaction remain unclear. We analyzed the expression and alteration profiles of ATAD2, along with its diagnostic and prognostic role in pan-can...
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Nature Portfolio
2024-09-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-73274-2 |
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| author | Zhecheng Li Yaxin Zhao Peng Huang Zhaoyi Wu Dengjie Ouyang Adolphus Osei Nyarko Lei Ai Zhejia Zhang Shi Chang |
| author_facet | Zhecheng Li Yaxin Zhao Peng Huang Zhaoyi Wu Dengjie Ouyang Adolphus Osei Nyarko Lei Ai Zhejia Zhang Shi Chang |
| author_sort | Zhecheng Li |
| collection | DOAJ |
| description | Abstract ATAD2 (ATPase Family AAA Domain-Containing 2) is highly expressed across varies tumor types, yet its common roles in tumor progression and immune interaction remain unclear. We analyzed the expression and alteration profiles of ATAD2, along with its diagnostic and prognostic role in pan-cancer, utilizing TCGA, GTEx, CPTAC, HPA, and cBioPortal databases. Furthermore, we examined the relationship between ATAD2 and immune infiltration utilizing single-cell sequencing data and TCGA database. Additionally, the expression and oncogenic functions of ATAD2 were verified in papillary thyroid carcinoma (PTC) through MTT, wound-healing, transwell, and flow cytometry assays. Our results revealed significant overexpression of ATAD2 in most cancers, strongly associated with poor prognosis. Amplification was the most frequent alteration type of ATAD2, with its mutation correlating with improved overall survival. ATAD2 was positively correlated with multiple inhibitory immune checkpoints and closely associated with the immunosuppressive microenvironment, particularly in PTC. In vitro experiments demonstrated that ATAD2 promoted the proliferation, migration, and invasion of PTC cells by activating the PI3K-AKT pathway and modulating the G1/S cell cycle checkpoint. Collectively, ATAD2 holds promise as a biomarker for pan-cancer diagnosis and prognosis, as well as a predictor of immunotherapeutic responsiveness and a therapeutic target to enhance the efficacy of existing anti-tumor immune therapies. |
| format | Article |
| id | doaj-art-8d4d1a984c09419c807ec656469e6b26 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-8d4d1a984c09419c807ec656469e6b262025-01-05T12:29:11ZengNature PortfolioScientific Reports2045-23222024-09-0114112010.1038/s41598-024-73274-2Pan-cancer analysis of the immunological and oncogenic roles of ATAD2 with verification in papillary thyroid carcinomaZhecheng Li0Yaxin Zhao1Peng Huang2Zhaoyi Wu3Dengjie Ouyang4Adolphus Osei Nyarko5Lei Ai6Zhejia Zhang7Shi Chang8Department of General Surgery, Xiangya Hospital, Central South UniversityDepartment of General Surgery, Xiangya Hospital, Central South UniversityDepartment of General Surgery, Xiangya Hospital, Central South UniversityDepartment of Thyroid and Breast Surgery, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Human Normal UniversityDepartment of General Surgery, Xiangya Hospital, Central South UniversityDepartment of General Surgery, Xiangya Hospital, Central South UniversityDepartment of General Surgery, Xiangya Hospital, Central South UniversityDepartment of General Surgery, Xiangya Hospital, Central South UniversityDepartment of General Surgery, Xiangya Hospital, Central South UniversityAbstract ATAD2 (ATPase Family AAA Domain-Containing 2) is highly expressed across varies tumor types, yet its common roles in tumor progression and immune interaction remain unclear. We analyzed the expression and alteration profiles of ATAD2, along with its diagnostic and prognostic role in pan-cancer, utilizing TCGA, GTEx, CPTAC, HPA, and cBioPortal databases. Furthermore, we examined the relationship between ATAD2 and immune infiltration utilizing single-cell sequencing data and TCGA database. Additionally, the expression and oncogenic functions of ATAD2 were verified in papillary thyroid carcinoma (PTC) through MTT, wound-healing, transwell, and flow cytometry assays. Our results revealed significant overexpression of ATAD2 in most cancers, strongly associated with poor prognosis. Amplification was the most frequent alteration type of ATAD2, with its mutation correlating with improved overall survival. ATAD2 was positively correlated with multiple inhibitory immune checkpoints and closely associated with the immunosuppressive microenvironment, particularly in PTC. In vitro experiments demonstrated that ATAD2 promoted the proliferation, migration, and invasion of PTC cells by activating the PI3K-AKT pathway and modulating the G1/S cell cycle checkpoint. Collectively, ATAD2 holds promise as a biomarker for pan-cancer diagnosis and prognosis, as well as a predictor of immunotherapeutic responsiveness and a therapeutic target to enhance the efficacy of existing anti-tumor immune therapies.https://doi.org/10.1038/s41598-024-73274-2ATAD2Pan-cancerPapillary thyroid carcinomaTherapeutic targetTumor immune microenvironment |
| spellingShingle | Zhecheng Li Yaxin Zhao Peng Huang Zhaoyi Wu Dengjie Ouyang Adolphus Osei Nyarko Lei Ai Zhejia Zhang Shi Chang Pan-cancer analysis of the immunological and oncogenic roles of ATAD2 with verification in papillary thyroid carcinoma Scientific Reports ATAD2 Pan-cancer Papillary thyroid carcinoma Therapeutic target Tumor immune microenvironment |
| title | Pan-cancer analysis of the immunological and oncogenic roles of ATAD2 with verification in papillary thyroid carcinoma |
| title_full | Pan-cancer analysis of the immunological and oncogenic roles of ATAD2 with verification in papillary thyroid carcinoma |
| title_fullStr | Pan-cancer analysis of the immunological and oncogenic roles of ATAD2 with verification in papillary thyroid carcinoma |
| title_full_unstemmed | Pan-cancer analysis of the immunological and oncogenic roles of ATAD2 with verification in papillary thyroid carcinoma |
| title_short | Pan-cancer analysis of the immunological and oncogenic roles of ATAD2 with verification in papillary thyroid carcinoma |
| title_sort | pan cancer analysis of the immunological and oncogenic roles of atad2 with verification in papillary thyroid carcinoma |
| topic | ATAD2 Pan-cancer Papillary thyroid carcinoma Therapeutic target Tumor immune microenvironment |
| url | https://doi.org/10.1038/s41598-024-73274-2 |
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