Faculty, Staff and Student Publications

Language

English

Publication Date

1-9-2026

Journal

JCI Insight

DOI

10.1172/jci.insight.191990

PMID

41480746

PMCID

PMC12890526

PubMedCentral® Posted Date

1-9-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Although well-differentiated thyroid carcinoma (WDTC) is characterized by a robust treatment response, aggressive subtypes, such as anaplastic thyroid carcinoma (ATC), remain highly lethal. To understand thyroid cancer evolution in both children and adults, we analyzed single-cell transcriptomes of 423,733 cells from 81 samples and spatially resolved key tumor and microenvironment populations across 28 tumors with spatial transcriptomics, including rare and unique composite WDTC/ATC tumors and pediatric diffuse sclerosing thyroid carcinomas. Additionally, we identified gene signatures of stromal cell populations in 5 large thyroid cancer bulk RNA-sequencing cohorts. Through this multi-institutional effort, we defined a population of POSTN+ myofibroblast cancer-associated fibroblasts (myCAFs) that are intimately associated with invasive tumor cells and correlate with poor prognosis, lymph node metastasis, and disease progression in thyroid carcinoma. We also revealed a population of inflammatory CAFs that are distant to tumor cells and are found in the inflammatory stromal microenvironment of autoimmune thyroiditis. Together, our study provides spatial profiling of thyroid cancer evolution in samples with mixed WDTC/ATC histopathology and identifies a prognostic myCAF subtype with potential clinical utility in predicting aggressive disease in both children and adults.

Keywords

Humans, Thyroid Neoplasms, Single-Cell Analysis, Transcriptome, Prognosis, Tumor Microenvironment, Disease Progression, Female, Child, Male, Adult, Cancer-Associated Fibroblasts, Middle Aged, Thyroid Carcinoma, Anaplastic, Gene Expression Profiling, Genetics, Oncology, Cancer, Head and neck cancer, Thyroid disease

Published Open-Access

yes

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