Section of Endocrine Surgery, Department of General, Visceral and Transplantation Surgery, University Medical Centre, Johannes Gutenberg University Mainz, Mainz, Germany.
Institute of Pathology, University Medical Centre, Johannes Gutenberg University Mainz, Mainz, Germany.
Genes Chromosomes Cancer. 2024 Aug;63(8):e23256. doi: 10.1002/gcc.23256.
Papillary thyroid carcinoma (PTC), the most common malignancy of follicular cell derivation, is generally associated with good prognosis. Nevertheless, it is important to identify patients with aggressive PTCs and unfavorable outcome. Molecular markers such as BRAF mutation and TERT promoter mutations have been proposed for risk stratification. While TERT promoter mutations have been frequently associated with aggressive PTCs, the association of BRAF mutation with increased recurrence and mortality is less clear and has been controversially discussed. The aim of the present study was to analyze whether differentially expressed genes can predict BRAF mutations as well as TERT promoter mutations in PTCs. RNA sequencing identified a large number of differentially expressed genes between BRAF and BRAF PTCs. Of those, AHNAK2, DCSTAMP, and FN1 could be confirmed in a larger cohort (n = 91) to be significantly upregulated in BRAF mutant PTCs using quantitative RT-PCR. Moreover, individual PTC expression values of DCSTAMP and FN1 were able to predict the BRAF mutation status with high sensitivity and specificity. The expression of TERT was detected in all PTCs harboring TERT promoter mutations and in 19% of PTCs without TERT promoter mutations. Tumors with both TERT expression and TERT promoter mutations were particularly associated with aggressive clinicopathological features and a shorter recurrence-free survival. Altogether, it will be interesting to explore the biological function of AHNAK2, DCSTAMP, and FN1 in PTC in more detail. The analysis of their expression patterns could allow the characterization of PTC subtypes and thus enabling a more individualized surgical and medical treatment.
甲状腺乳头状癌（PTC）是最常见的滤泡细胞来源的恶性肿瘤，通常预后良好。然而，识别具有侵袭性和不良预后的 PTC 患者是非常重要的。已经提出了分子标志物，如 BRAF 突变和 TERT 启动子突变，用于风险分层。虽然 TERT 启动子突变与侵袭性 PTC 密切相关，但 BRAF 突变与复发和死亡率增加的相关性尚不清楚，并且存在争议。本研究旨在分析差异表达基因是否可以预测 PTC 中的 BRAF 突变和 TERT 启动子突变。RNA 测序鉴定出 BRAF 和 BRAF PTC 之间大量差异表达的基因。在更大的队列（n=91）中，使用定量 RT-PCR 证实 AHNAK2、DCSTAMP 和 FN1 在 BRAF 突变型 PTC 中显著上调。此外，DCSTAMP 和 FN1 的个体 PTC 表达值能够以高灵敏度和特异性预测 BRAF 突变状态。所有携带 TERT 启动子突变的 PTC 以及 19%无 TERT 启动子突变的 PTC 中均检测到 TERT 的表达。同时具有 TERT 表达和 TERT 启动子突变的肿瘤与侵袭性临床病理特征和较短的无复发生存期特别相关。总的来说，深入探讨 AHNAK2、DCSTAMP 和 FN1 在 PTC 中的生物学功能将很有趣。分析它们的表达模式可以使 PTC 亚型得以表征，从而实现更个体化的手术和治疗。
