Mitochondrial Proteome Defined Molecular Pathological Characteristics of Oncocytic Thyroid Tumors.

IF 11.3 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Endocrine Pathology Pub Date : 2024-11-04 DOI:10.1007/s12022-024-09834-z

Lu Li, Likun Zhang, Wenhao Jiang, Zhiqiang Gui, Zhihong Wang, Hao Zhang, Yi He, Yi Zhu, Tiannan Guo, Haixia Guan, Zhiyan Liu, Yaoting Sun, Jianqing Gao

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Abstract

Oncocytic thyroid tumors are characterized by an elevated mitochondrial density within the cells, distinguishing them from other thyroid tumors, exhibit distinct clinical behaviors, including increased invasiveness and iodine therapy resistance. However, the proteomic alterations in oncocytic thyroid tumors remain inadequately characterized. In this study, we analyzed 156 Asian patients with oncocytic thyroid adenomas (OA) and carcinomas (OCA) to explore their clinical, genetic, and proteomic features. Genetic testing of 73 samples revealed frequent mutations in TERT, NRAS, EIF1AX, EZH1, and HRAS, with TERT promoter mutations being exclusive to OCAs. Proteomic analysis identified 66 mitochondrial-specific proteins significantly highly expressed in oncocytic tumors than in non-oncocytic tumors. This led to the development of a thyroid oncocytic score (TOS) to quantify oncocytic characteristics. Among these proteins, isocitrate dehydrogenase 2 (IDH2) was substantially overexpressed in oncocytic tumors and further confirmed by immunohistochemistry in oncocytic tumor slides (n = 41) and non-oncocytic tumor slides (n = 40). Moreover, IDH2 is significantly overexpressed in OCA compared to OA highlighting its potential as a biomarker for differential diagnosis of oncocytic tumors and malignancy. These findings improve the understanding of oncocytic thyroid tumors molecular pathology and suggest IDH2 as a valuable marker for clinical management.

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线粒体蛋白质组定义了肿瘤性甲状腺肿瘤的分子病理学特征

肿瘤细胞性甲状腺肿瘤的特点是细胞内线粒体密度升高，有别于其他甲状腺肿瘤，表现出独特的临床表现，包括侵袭性增加和碘治疗耐药。然而，肿瘤细胞甲状腺瘤的蛋白质组学改变特征仍不充分。在这项研究中，我们分析了156名患有甲状腺肿瘤细胞腺瘤（OA）和癌（OCA）的亚洲患者，探讨了他们的临床、遗传和蛋白质组学特征。对73份样本的基因检测发现，TERT、NRAS、EIF1AX、EZH1和HRAS经常发生突变，其中TERT启动子突变是OCA独有的。蛋白质组分析发现，66种线粒体特异性蛋白在肿瘤细胞中的表达明显高于非肿瘤细胞。因此，开发了甲状腺肿瘤细胞评分（TOS）来量化肿瘤细胞特征。在这些蛋白中，异柠檬酸脱氢酶2（IDH2）在肿瘤细胞肿瘤中大量过表达，肿瘤细胞肿瘤切片（n = 41）和非肿瘤细胞肿瘤切片（n = 40）的免疫组化进一步证实了这一点。此外，与 OA 相比，IDH2 在 OCA 中明显过表达，这凸显了其作为鉴别诊断肿瘤细胞瘤和恶性肿瘤的生物标记物的潜力。这些发现加深了人们对肿瘤细胞性甲状腺肿瘤分子病理学的了解，并建议将IDH2作为临床治疗的重要标志物。

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来源期刊

Endocrine Pathology 医学-病理学

CiteScore

12.30

自引率

20.50%

发文量

审稿时长

>12 weeks

期刊介绍： Endocrine Pathology publishes original articles on clinical and basic aspects of endocrine disorders. Work with animals or in vitro techniques is acceptable if it is relevant to human normal or abnormal endocrinology. Manuscripts will be considered for publication in the form of original articles, case reports, clinical case presentations, reviews, and descriptions of techniques. Submission of a paper implies that it reports unpublished work, except in abstract form, and is not being submitted simultaneously to another publication. Accepted manuscripts become the sole property of Endocrine Pathology and may not be published elsewhere without written consent from the publisher. All articles are subject to review by experienced referees. The Editors and Editorial Board judge manuscripts suitable for publication, and decisions by the Editors are final.