Single‐Cell Atlas Reveals Tumorigenic Profiles and Immune Dynamics of Adrenal Incidentalomas
Adrenal incidentalomas (AIs) are commonly detected endocrine lesions, identified during imaging for unrelated conditions. These lesions exhibit considerable heterogeneity and diverse clinical outcomes. This study employed single-cell RNA sequencing to investigate tumorigenic characteristics of AIs, including non-functional adrenocortical adenomas, Conn's syndrome, and pheochromocytomas. Through integrating public datasets, 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-oncogene (MYCN)-positive 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-positive (CD8+) T cells, appear to promote immune activation and infiltration in malignant tumors. Overall, this study enhances the understanding of adrenal adenoma heterogeneity, revealing crucial transcriptional profiles, immune interactions, and clinically relevant candidate biomarkers.
Authors
- Guangmin Zheng (ORCID: https://orcid.org/0000-0002-3781-170X)
- Daofu Cheng
- Meng Wang (ORCID: https://orcid.org/0000-0003-0221-0653)
- Feng Tian (ORCID: https://orcid.org/0000-0003-3552-4536)
- Yujing Sun (ORCID: https://orcid.org/0000-0002-4886-0005)
- Kan Gong (ORCID: https://orcid.org/0000-0001-7195-677X)
- Liu Liu (ORCID: https://orcid.org/0000-0003-3566-0212)
- Bing Liu (ORCID: https://orcid.org/0000-0002-6825-3536)
- Lin Li (ORCID: https://orcid.org/0000-0002-2158-7096)
- Zheng Zhang (ORCID: https://orcid.org/0000-0003-1961-7070)
- Chao Zhang (ORCID: https://orcid.org/0000-0001-6418-8370)
- Shiwei Chen (ORCID: https://orcid.org/0000-0002-0812-5065)
- Lin Yuan (ORCID: https://orcid.org/0000-0002-6583-7333)
- Tuo Li (ORCID: https://orcid.org/0000-0002-6691-7423)
- Fuqiang Liu (ORCID: https://orcid.org/0000-0002-9950-3673)
- Qi Yu (ORCID: https://orcid.org/0000-0002-7786-7441)
- Ruxing Zhao (ORCID: https://orcid.org/0000-0002-8893-1007)
- Xiaoyong Hu (ORCID: https://orcid.org/0009-0006-8917-3793)
- Xiangdong Fang (ORCID: https://orcid.org/0000-0002-6628-8620)
Institutions
- Hebei University of Engineering (CN)
- Second Military Medical University (CN)
- Shanghai Jiao Tong University (CN)
- Chinese Academy of Sciences (CN)
- Peking University (CN)
- Beijing Institute of Genomics (CN)
- Shanghai Changzheng Hospital (CN)
- Songjiang District Central Hospital (CN)
- Peking University First Hospital (CN)
- Shanghai First People's Hospital (CN)
- Eastern Hepatobiliary Surgery Hospital (CN)
- Shanghai Sixth People's Hospital (CN)
- Qilu Hospital of Shandong University (CN)
Publication Details
- Journal
- Advanced Science
- Published
- 2025-04-07
- DOI
- https://doi.org/10.1002/advs.202413493
- Citations
- 2
- Primary Topic
- Hormonal Regulation and Hypertension
- Type
- article
- Field-Weighted Citation Impact
- 2.59
Funders
- National Natural Science Foundation of China
- Shanghai Municipal Education Commission
- Science and Technology Commission of Shanghai Municipality
- Shanghai Clinical Research Center
- National Science and Technology Major Project