Wang Meng, Zheng Guangmin, Hu Xiaoyong, Tian Feng, Li Tuo, Zhang Zheng, Gong Kan, Chen Shiwei, Yuan Lin, Qi Yu, Li Lin, Cheng Daofu, Liu Liu, Liu Fuqiang, Sun Yujing, Fang Xiangdong, Zhao Ruxing, Liu Bing, Zhang Chao
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.
Adv Sci (Weinh). 2025 Jun;12(22):e2413493. doi: 10.1002/advs.202413493. Epub 2025 Apr 7.
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.
肾上腺偶发瘤（AIs）是常见的内分泌病变，在因无关疾病进行影像学检查时被发现。这些病变表现出相当大的异质性和多样的临床结果。本研究采用单细胞RNA测序来研究肾上腺偶发瘤的致瘤特征，包括无功能肾上腺皮质腺瘤、原发性醛固酮增多症和嗜铬细胞瘤。通过整合公共数据集，分析了302696个细胞。三种肾上腺皮质细胞亚型表现出与肿瘤发生相关的基因表达模式。簇集蛋白成为肾上腺皮质腺瘤的潜在生物标志物。肾上腺皮质肿瘤细胞显示激素分泌失调，转录因子类固醇生成因子1（SF1）显著上调，这将皮质肿瘤与髓质肿瘤区分开来。在嗜铬细胞瘤中，MYCN原癌基因（MYCN）阳性簇与较差的生存率相关。免疫微环境分析揭示了肿瘤进展中的特定免疫亚型及其作用。具体而言，髓样细胞可能调节良性肿瘤，而淋巴细胞，如CD8阳性（CD8+）T细胞，似乎促进恶性肿瘤中的免疫激活和浸润。总体而言，本研究增进了对肾上腺腺瘤异质性的理解，揭示了关键的转录谱、免疫相互作用以及临床相关的候选生物标志物。
