Differential expression profiles of immunoregulatory genes in anaplastic thyroid carcinomas with a coexistent papillary carcinoma component

TL;DR

This study compares gene and miRNA expression in aggressive thyroid cancers to understand immune regulation differences and identify potential biomarkers.

Contribution

The study identifies specific deregulated genes and miRNAs in anaplastic thyroid carcinoma compared to papillary thyroid carcinoma and poorly differentiated thyroid carcinoma.

Findings

Five genes were downregulated and six genes were upregulated in anaplastic thyroid carcinoma compared to papillary thyroid carcinoma.

54 miRNAs were significantly upregulated in anaplastic thyroid carcinoma, with several targeting the MAP3K1 gene in the MAPK signaling pathway.

Over 200 genes were differentially expressed between poorly differentiated thyroid carcinoma and anaplastic thyroid carcinoma, affecting major immune-related pathways.

Abstract

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.

The online version contains supplementary material available at 10.1007/s00428-025-04262-8.

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