Haq Faridul, Bychkov Andrey, Mete Ozgur, Jeon Sora, Jung Chan Kwon
Department of Hospital Pathology, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpo-daero, Seocho-Gu, Seoul, 06591, Republic of Korea.
Department of Biomedicine and Health Sciences, The Catholic University of Korea, Seoul, 06591, Republic of Korea.
Endocr Pathol. 2025 Apr 17;36(1):14. doi: 10.1007/s12022-025-09858-z.
Anaplastic thyroid carcinoma (ATC) is an aggressive malignancy with a poor prognosis. Despite its rarity, identifying predictive molecular markers that distinguish ATC from follicular cell-derived non-anaplastic thyroid carcinomas is critical for improving diagnosis and treatment strategies. This study aimed to identify and validate key mRNA and protein markers associated with ATC progression and dedifferentiation. We performed spatial transcriptomic analysis on an index case of ATC coexisting with papillary thyroid carcinoma (PTC) and identified eight differentially expressed mRNA markers. These findings were validated in a large cohort using immunohistochemistry on tissue microarrays across various thyroid tumor types, including follicular adenoma, PTC, poorly differentiated thyroid carcinoma, medullary thyroid carcinoma, and ATC. Additionally, the impact of BRAF p.V600E mutation status on these markers was evaluated. COL7A1, LAMC2, SPHK1, and SRPX2 mRNA and protein levels were significantly overexpressed in ATCs. Conversely, CD24, EPHX1, GPX3, and RBM47 mRNA and protein levels were markedly downregulated in ATCs. Functional enrichment analysis, based on mRNA expression data, identified the role of these proteins in tumor invasion, epithelial-mesenchymal transition, extracellular matrix remodeling, and immune evasion. The expression levels of these markers were independent of BRAF p.V600E mutation status, highlighting their potential as diagnostic markers. In summary, this study identified eight molecular markers that can distinguish ATC from other thyroid tumors. The validation of these markers at both the mRNA and protein levels underscores their clinical relevance in ATC diagnosis and tumor characterization. These findings provide a foundation for future biomarker-driven diagnostic and therapeutic strategies for ATC.
间变性甲状腺癌（ATC）是一种侵袭性恶性肿瘤，预后较差。尽管其罕见，但识别区分ATC与滤泡细胞源性非间变性甲状腺癌的预测性分子标志物对于改善诊断和治疗策略至关重要。本研究旨在识别和验证与ATC进展和去分化相关的关键mRNA和蛋白质标志物。我们对一例与乳头状甲状腺癌（PTC）共存的ATC索引病例进行了空间转录组分析，并确定了八个差异表达的mRNA标志物。这些发现通过对包括滤泡性腺瘤、PTC、低分化甲状腺癌、髓样甲状腺癌和ATC在内的各种甲状腺肿瘤类型的组织微阵列进行免疫组织化学在一个大型队列中得到验证。此外，评估了BRAF p.V600E突变状态对这些标志物的影响。COL7A1、LAMC2、SPHK1和SRPX2的mRNA和蛋白质水平在ATC中显著过表达。相反，CD24、EPHX1、GPX3和RBM47的mRNA和蛋白质水平在ATC中明显下调。基于mRNA表达数据的功能富集分析确定了这些蛋白质在肿瘤侵袭、上皮-间质转化、细胞外基质重塑和免疫逃逸中的作用。这些标志物的表达水平与BRAF p.V600E突变状态无关，突出了它们作为诊断标志物的潜力。总之，本研究确定了八个可区分ATC与其他甲状腺肿瘤的分子标志物。这些标志物在mRNA和蛋白质水平的验证强调了它们在ATC诊断和肿瘤特征描述中的临床相关性。这些发现为未来基于生物标志物的ATC诊断和治疗策略奠定了基础。
