Orlando Giulia, Napoli Francesca, Zambelli Vanessa, Maletta Francesca, Capella Giulia, Duregon Eleonora, Volante Marco, Papotti Mauro
Department of Oncology, University of Turin, San Luigi Hospital, Regione Gonzole 10, Orbassano, Turin, 10043, Italy.
Pathology Unit, Città Della Salute E Della Scienza Hospital, Turin, Italy.
Virchows Arch. 2025 Sep 18. doi: 10.1007/s00428-025-04262-8.
Limited data exist on the immunoregulatory mechanisms involv ed in thyroid cancer, particularly in aggressive forms. This study aimed at identifying the expression profiles of immune-related genes and miRNAs in anaplastic (ATC) and poorly differentiated thyroid carcinomas (PDTC) associated with papillary carcinoma (PTC) components. Immune-related genes were investigated using the nCounter® PanCancer Immune Profiling Panel in separate ATC and PTC components of 12 cases, and in PDTC component only of nine additional cases associated with PTC. Global miRNAs profiling was also analyzed separately in ATC and PTC components of 8 out of the 12 cases. Comparative analysis between ATC and matched PTC components revealed largely stable gene expression patterns, with only a few genes deregulated. Of these, five genes (MAP3K1, PRKCD, CYFIP2, BLNK, and EPCAM) were downregulated, while six (RIPK2, ITGB1, CCL3L1, ITGA5, PLAUR, and TICAM2) were upregulated in ATC. Furthermore, 54 miRNAs were significantly upregulated in ATC, as compared to PTC components. One of the most regulated pathways was the MAPK signaling, with six of these deregulated miRNAs targeting the MAP3K1 gene. Comparing ATC and PDTC, over 200 genes were differentially expressed between PDTC and ATC samples, involving all major immune-related pathways, with a consistent downregulation in PDTC. In conclusion, ATC displays high levels of expression of immunoregulatory genes as compared to PDTC. Moreover, a subset of genes and miRNAs is significantly de-regulated along progression from PTC to ATC, suggesting their potential role as biomarkers and involvement in key functional mechanisms.
关于甲状腺癌，尤其是侵袭性甲状腺癌中涉及的免疫调节机制的数据有限。本研究旨在确定间变性甲状腺癌（ATC）和低分化甲状腺癌（PDTC）与乳头状癌（PTC）成分相关的免疫相关基因和微小RNA（miRNA）的表达谱。使用nCounter®泛癌免疫分析面板对12例病例的单独ATC和PTC成分以及另外9例与PTC相关病例的仅PDTC成分进行免疫相关基因研究。还对12例中的8例的ATC和PTC成分分别进行了全局miRNA谱分析。ATC与匹配的PTC成分之间的比较分析显示基因表达模式基本稳定，只有少数基因失调。其中，5个基因（MAP3K1、PRKCD、CYFIP2、BLNK和EPCAM）在ATC中下调，而6个基因（RIPK2、ITGB1、CCL3L1、ITGA5、PLAUR和TICAM2）在ATC中上调。此外，与PTC成分相比，54种miRNA在ATC中显著上调。调控最明显的途径之一是丝裂原活化蛋白激酶（MAPK）信号传导，这些失调的miRNA中有6个靶向MAP3K1基因。比较ATC和PDTC，PDTC和ATC样本之间有超过200个基因差异表达，涉及所有主要的免疫相关途径，PDTC中持续下调。总之，与PDTC相比，ATC显示出免疫调节基因的高表达水平。此外，从PTC进展到ATC的过程中，一部分基因和miRNA显著失调，表明它们作为生物标志物的潜在作用以及参与关键功能机制。
