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

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.

In this pilot study, bulk RNA sequencing of 19 specimens (10 TC, 9 NG) allowed classification into four tumour microenvironment (TME) subgroups.

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.

These findings suggest that transcriptomic convergence largely reflects shared inflammatory programmes, whereas stromal remodelling identifies a candidate tumour-associated stromal programme.