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These lesions exhibit considerable heterogeneity and diverse clinical outcomes. This study employed single\u2010cell RNA sequencing to investigate tumorigenic characteristics of AIs, including non\u2010functional adrenocortical adenomas, Conn's syndrome, and pheochromocytomas. Through integrating public\u00a0datasets, 302 696 cells are analyzed. Three adrenocortical cell subtypes exhibit gene expression patterns linked to tumorigenesis. Clusterin emerges as a potential biomarker for adrenocortical adenomas. Adrenocortical tumor cells show dysregulated hormone secretion and transcription factor steroidogenic factor 1 (SF1) is significantly upregulated, distinguishing cortical from medullary tumors. In pheochromocytomas, a MYCN proto\u2010oncogene (MYCN)\u2010positive cluster correlates with poorer survival. Immune microenvironment analysis reveals specific immune subtypes and roles in tumor progression. Specifically, myeloid cells may regulate benign tumors, while lymphoid cells, such as CD8\u2010positive (CD8+) T cells, appear to promote immune activation and infiltration in malignant tumors. Overall, this\u00a0study enhances the understanding of adrenal adenoma heterogeneity, revealing crucial transcriptional profiles, immune interactions, and clinically relevant candidate biomarkers.<\/jats:p>","DOI":"10.1002\/advs.202413493","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T04:56:12Z","timestamp":1744001772000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Single\u2010Cell Atlas Reveals Tumorigenic Profiles and Immune Dynamics of Adrenal Incidentalomas"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0221-0653","authenticated-orcid":false,"given":"Meng","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Orthopedics and Precision Research Center for Refractory Diseases Shanghai General Hospital Shanghai Jiao Tong University School of Medicine  Shanghai 200080 China"},{"name":"Department of Endocrinology Songjiang Research Institute Shanghai Key Laboratory of Emotions and Affective Disorders (LEAD) Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai 201600 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangmin","family":"Zheng","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Genome Sciences and Information Beijing Institute of Genomics Chinese Academy of Sciences\/China National Center for Bioinformation  Beijing 100101 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyong","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Urology Shanghai Jiao Tong University Affiliated Sixth People's Hospital  Shanghai 200000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Tian","sequence":"additional","affiliation":[{"name":"Hebei Key Laboratory of Medical Data Science Institute of Biomedical Informatics School of Medicine Hebei University of Engineering  Handan Hebei Province 056009 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuo","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Shanghai Changzheng Hospital  Shanghai 200003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology School of Basic Medical Sciences Department of Urology Peking University First Hospital Peking University Health Science Center  Beijing 100035 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kan","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology School of Basic Medical Sciences Department of Urology Peking University First Hospital Peking University Health Science Center  Beijing 100035 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiwei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology School of Basic Medical Sciences Department of Urology Peking University First Hospital Peking University Health Science Center  Beijing 100035 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Pathology Shanghai General Hospital Shanghai Jiao Tong University School of Medicine  Shanghai 201620 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Pathology Shanghai General Hospital Shanghai Jiao Tong University School of Medicine  Shanghai 201620 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Urology Eastern Hepatobiliary Surgery Hospital  Shanghai 201805 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daofu","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Precision Research Center for Refractory Diseases Shanghai General Hospital Shanghai Jiao Tong University School of Medicine  Shanghai 200080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai Yuhui Pharmaceutical Technology (Group) Co., Ltd.  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