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journal article·2025-06Open access

Single‐Cell Atlas Reveals Tumorigenic Profiles and Immune Dynamics of Adrenal Incidentalomas

Meng Wang, Guangmin Zheng, Xiaoyong Hu, Feng Tian, Tuo Li, Zheng Zhang, Kan Gong, Shiwei Chen, Lin Yuan, Yu Qi, Lin Li, Daofu Cheng, Liu Liu, Fuqiang Liu, Yujing Sun, Xiangdong Fang, Ruxing Zhao, Bing Liu, Chao Zhang

Advanced Science· Volume 12· Issue 22
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Abstract

Abstract 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.
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Research context

OpenAlex topics: Hormonal Regulation and Hypertension · Single-cell and spatial transcriptomics · Adrenal and Paraganglionic Tumors

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Orthopedics and Precision Research Center for Refractory Diseases Shanghai General Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200080 China

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

CAS Key Laboratory of Genome Sciences and Information Beijing Institute of Genomics Chinese Academy of Sciences/China National Center for Bioinformation Beijing 100101 China

Department of Urology Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai 200000 China

Hebei Key Laboratory of Medical Data Science Institute of Biomedical Informatics School of Medicine Hebei University of Engineering Handan Hebei Province 056009 China

Department of Endocrinology Shanghai Changzheng Hospital Shanghai 200003 China

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

Department of Pathology Shanghai General Hospital Shanghai Jiao Tong University School of Medicine Shanghai 201620 China

Department of Urology Eastern Hepatobiliary Surgery Hospital Shanghai 201805 China

Shanghai Yuhui Pharmaceutical Technology (Group) Co., Ltd. Shanghai 201203 China

Department of Endocrinology and Metabolism Qilu Hospital of Shandong University Shandong Provincial Key Laboratory of Spatiotemporal Regulation and Precision Intervention in Endocrine and Metabolic Diseases Shandong University Jinan 250012 China

Funding

National Natural Science Foundation of China · Innovative Research Team of High-level Local University in Shanghai

References (55)

Show source-provided references
1. 10.1210/endrev/bnaa00810.1210/endrev/bnaa008 ↗
2. 10.1056/NEJMcp203111210.1056/NEJMcp2031112 ↗
3. 10.1056/NEJMcp06547010.1056/NEJMcp065470 ↗
4. 10.3389/fcell.2015.0004510.3389/fcell.2015.00045 ↗
5. 10.1038/ng.295310.1038/ng.2953 ↗
6. 10.1126/sciadv.abd331110.1126/sciadv.abd3311 ↗
7. 10.1038/s41588-021-00806-110.1038/s41588-021-00806-1 ↗
8. 10.1073/pnas.202235011810.1073/pnas.2022350118 ↗
9. 10.1016/j.ccell.2020.08.01410.1016/j.ccell.2020.08.014 ↗
10. 10.1016/j.celrep.2022.11145510.1016/j.celrep.2022.111455 ↗
11. Zhang X. · eLife · 2021 · 10
12. 10.1210/clinem/dgac39410.1210/clinem/dgac394 ↗
13. 10.7554/eLife.6843610.7554/eLife.68436 ↗
14. 10.7554/eLife.8758610.7554/eLife.87586 ↗
15. 10.1016/j.mce.2011.08.04110.1016/j.mce.2011.08.041 ↗
16. 10.1016/j.molmet.2024.10195410.1016/j.molmet.2024.101954 ↗
17. 10.1161/HYPERTENSIONAHA.117.0999110.1161/HYPERTENSIONAHA.117.09991 ↗
18. 10.1016/j.jsbmb.2010.12.00110.1016/j.jsbmb.2010.12.001 ↗
19. 10.1038/nrendo.2014.16610.1038/nrendo.2014.166 ↗
20. 10.1038/nrc118710.1038/nrc1187 ↗
21. 10.1016/j.molcel.2010.09.02210.1016/j.molcel.2010.09.022 ↗
22. 10.1002/j.2040-4603.2014.tb00573.x10.1002/j.2040-4603.2014.tb00573.x ↗
23. 10.1016/j.jsbmb.2014.10.00910.1016/j.jsbmb.2014.10.009 ↗
24. 10.1056/NEJMra190978610.1056/NEJMra1909786 ↗
25. 10.1530/EJE-08-071110.1530/EJE-08-0711 ↗
26. 10.1016/0166-2236(92)90190-J10.1016/0166-2236(92)90190-J ↗
27. 10.2353/ajpath.2006.05086710.2353/ajpath.2006.050867 ↗
28. 10.1016/S0960-0760(03)00217-610.1016/S0960-0760(03)00217-6 ↗
29. 10.1681/ASN.201501009310.1681/ASN.2015010093 ↗
30. 10.1016/j.mce.2010.11.02410.1016/j.mce.2010.11.024 ↗
31. 10.1093/nar/gkt65810.1093/nar/gkt658 ↗
32. 10.1038/nmeth.446310.1038/nmeth.4463 ↗
33. 10.1007/BF0055479410.1007/BF00554794 ↗
34. 10.1038/s41588-021-00806-110.1038/s41588-021-00806-1 ↗
35. 10.1038/nrc364810.1038/nrc3648 ↗
36. 10.1038/ng.86110.1038/ng.861 ↗
37. 10.1158/0008-5472.CAN-11-389110.1158/0008-5472.CAN-11-3891 ↗
38. 10.1016/j.xcrm.2022.10065710.1016/j.xcrm.2022.100657 ↗
39. 10.1016/j.celrep.2022.11119310.1016/j.celrep.2022.111193 ↗
40. 10.1038/s41596-020-0292-x10.1038/s41596-020-0292-x ↗
41. 10.1038/s41419-022-04552-y10.1038/s41419-022-04552-y ↗
42. 10.1038/s41419-021-03426-z10.1038/s41419-021-03426-z ↗
43. 10.1056/NEJMoa180877710.1056/NEJMoa1808777 ↗
44. 10.1007/s00262-004-0603-z10.1007/s00262-004-0603-z ↗
45. 10.1038/s41586-021-04183-x10.1038/s41586-021-04183-x ↗
46. 10.1681/ASN.201306057710.1681/ASN.2013060577 ↗
47. 10.1038/nrdp.2016.7810.1038/nrdp.2016.78 ↗
48. 10.1016/j.semcancer.2011.08.00110.1016/j.semcancer.2011.08.001 ↗
49. 10.1016/j.cell.2019.05.03110.1016/j.cell.2019.05.031 ↗
50. 10.1038/nmeth.446310.1038/nmeth.4463 ↗
51. 10.1089/omi.2011.011810.1089/omi.2011.0118 ↗
52. 10.1093/nar/gkac100010.1093/nar/gkac1000 ↗
53. 10.1101/gr.123930310.1101/gr.1239303 ↗
54. 10.3389/fgene.2022.86996710.3389/fgene.2022.869967 ↗
55. 10.1016/j.ccell.2022.10.00810.1016/j.ccell.2022.10.008 ↗