Single-cell RNA Sequencing Reveals the Heterogeneity in Differentiation Trajectory and Tumor Microenvironment Leading to More Aggressive Phenotypes of Papillary Thyroid Cancer in Children and Young Adult Patients

ABSTRACT: The tumor ecosystem heterogeneity of papillary thyroid carcinoma (PTC) is poorly characterized especially in children and young adult patients (CAYA-PTC). Here, we used single-cell RNA sequencing to profile transcriptomes map from eleven patients’ paratumors and localized tumors, covering comprehensive clinical courses of PTC. Compared with adult-PTC, CD4T_Tfh and CD8T_Tex cells were significantly higher in CAYA-PTC patients which closely related to metastasis. Along the differentiation trajectory, we discover three phenotypes of thyrocytes population (normal, BRAF-like, Fusion-like), whose composition shapes bulk molecular subtypes and tumor characteristics. Furthermore, our data identifies CAYA-PTC patients lack a “mild-state (BRAF-like)” malignant thyrocyte population. This different differentiation states indicates PTC cells quickly develop into invasion and metastasis in CAYA patients, while they gradually progress over a long time in adult patients. In addition, extracellular matrix cancer-associated fibroblasts(emCAFs_LAMP5) interact with endothelial cells and thyrocytes, ultimately promoting tumor angiogenesis and metastasis, which plays a more evident role in CAYA patients. FAP was highly expressed in emCAF_LAMP5 and positive correlated with LAMP5 in CAYA-PTC tissues. Therefore, ⁶⁸Ga-FAPI-PET have the potential to be used as a promising diagnostic method for CAYA patients with failed by traditional 18F-FDG-PET/CT. Together, our findings provide insight into the CAYA-PTC ecosystem that suggests distinct diagnostic, prognostic and therapeutic implications compared to adults.

ORGANISM(S): Homo sapiens

PROVIDER: GSE281736 | GEO | 2025/01/01

REPOSITORIES: GEO