Transcriptomic Convergence Reveals Tumour-Specific Stromal Remodelling in Immune-Enriched Papillary Thyroid Carcinoma
- 1Molecular Medicine Center, Department of Medical Chemistry and Biochemistry, Medical Faculty, Medical University of Sofia, 1431 Sofia, Bulgaria
- 2Department of Endocrinology, Medical Faculty, Medical University of Sofia, 1431 Sofia, Bulgaria
Abstract
Background: Although immune activation can occur in both papillary thyroid carcinoma (TC) and nodular goitre (NG), the transcriptional programmes distinguishing malignant from non-malignant immune-rich thyroid tissue remain poorly understood. Methods: In this pilot study, bulk RNA sequencing of 19 specimens (10 TC, 9 NG) allowed classification into four tumour microenvironment (TME) subgroups. Results: Immune deconvolution showed that TC Immune-Enriched tumours were characterised by cancer-associated fibroblast (CAF) enrichment rather than predominant lymphocytic infiltration. Differential expression analysis identified only nine genes distinguishing TC Immune-Enriched from NG Immune-High tissue, suggesting transcriptomic similarity between malignant and benign immune-activated states in this small cohort. To identify tumour-associated stromal programmes, we identified genes shared between immune-enriched versus immune-depleted comparisons in papillary TC and nodular goitre. This yielded a 441-gene candidate tumour-associated stromal programme enriched for collagen-containing extracellular matrix organisation and TGFβ-associated ECM-remodelling pathways, supported by WGCNA and protein-protein interaction analyses. In 456 TCGA-THCA carcinomas, stromal enrichment correlated inversely with thyroid differentiation and was highest in BRAF-like tumours and the tall-cell histological variant. Conclusions: These findings suggest that transcriptomic convergence largely reflects shared inflammatory programmes, whereas stromal remodelling identifies a candidate tumour-associated stromal programme.
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BibTeX
@article{petkova2026transcriptomic,
title = {{Transcriptomic Convergence Reveals Tumour-Specific Stromal Remodelling in Immune-Enriched Papillary Thyroid Carcinoma}},
author = {Veronika Petkova and Rumyana Dodova and Kalin Vidinov and Radka Kaneva},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18203406},
url = {https://www.mdpi.com/2072-6694/18/20/3406},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Transcriptomic Convergence Reveals Tumour-Specific Stromal Remodelling in Immune-Enriched Papillary Thyroid Carcinoma
AU - Veronika Petkova
AU - Rumyana Dodova
AU - Kalin Vidinov
AU - Radka Kaneva
PY - 2026
DA - 2026/10/01
JO - Cancers
DO - 10.3390/cancers18203406
UR - https://www.mdpi.com/2072-6694/18/20/3406
AB - Background: Although immune activation can occur in both papillary thyroid carcinoma (TC) and nodular goitre (NG), the transcriptional programmes distinguishing malignant from non-malignant immune-rich thyroid tissue remain poorly understood. Methods: In this pilot study, bulk RNA sequencing of 19 specimens (10 TC, 9 NG) allowed classification into four tumour microenvironment (TME) subgroups. Results: Immune deconvolution showed that TC Immune-Enriched tumours were characterised by cancer-associated fibroblast (CAF) enrichment rather than predominant lymphocytic infiltration. Differential expression analysis identified only nine genes distinguishing TC Immune-Enriched from NG Immune-High tissue, suggesting transcriptomic similarity between malignant and benign immune-activated states in this small cohort. To identify tumour-associated stromal programmes, we identified genes shared between immune-enriched versus immune-depleted comparisons in papillary TC and nodular goitre. This yielded a 441-gene candidate tumour-associated stromal programme enriched for collagen-containing extracellular matrix organisation and TGFβ-associated ECM-remodelling pathways, supported by WGCNA and protein-protein interaction analyses. In 456 TCGA-THCA carcinomas, stromal enrichment correlated inversely with thyroid differentiation and was highest in BRAF-like tumours and the tall-cell histological variant. Conclusions: These findings suggest that transcriptomic convergence largely reflects shared inflammatory programmes, whereas stromal remodelling identifies a candidate tumour-associated stromal programme.
SN - 2072-6694
ER -