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Peer-reviewedCC BY 4.0Cancers

Transcriptomic Convergence Reveals Tumour-Specific Stromal Remodelling in Immune-Enriched Papillary Thyroid Carcinoma

  1. 1Molecular Medicine Center, Department of Medical Chemistry and Biochemistry, Medical Faculty, Medical University of Sofia, 1431 Sofia, Bulgaria
  2. 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  -