Title : Transcriptomic analysis of papillary thyroid carcinoma in adolescents and young adults: Unveiling developmental differences in lymph node metastasis
Abstract:
Adolescents and young adults (AYA) with papillary thyroid carcinoma (PTC) exhibit more aggressive metastatic characteristics compared to adults (AD), despite having lower tumor proliferation rates. This study aims to identify molecular differences between AYA and AD PTCs through transcriptomic analysis and immunohistochemistry (IHC), and explore the reasons for the increased aggressiveness of cancer lesions in the AYA population.
The study conducted statistical analysis on RNA expression profiles from 501 patients in The Cancer Genome Atlas (TCGA) (categorized into AYA and AD groups), identifying clinical features that differed between the two groups. Differentially expressed genes (DEGs) of interest were selected using RNA sequencing in an independent cohort of 13 patients (7 AYA and 6 AD). Functional enrichment and topological analysis were used to identify core molecular features associated with age-related tumor aggressiveness, and IHC was used for validation.
We identified 239 core DEGs between AYA and AD PTC. Functional enrichment analysis highlighted the importance of cell adhesion, ion transmembrane transport, and cell signaling in tumor invasion. Key genes in AYA, including upregulated CXCR4, OPCML, and S100A2, and downregulated ATP1A3, CHL1, HLA-DRA, and IL-1 Beta, were found to be critical for the high invasiveness of the tumor. IL-1 Beta, CXCR4, and HLA-DRA were associated with immune cell infiltration.
PTC in AYA patients exhibits unique molecular characteristics with high metastatic potential. Incorporating age-specific molecular markers into clinical management can enhance diagnostic accuracy and facilitate the development of personalized treatment strategies for AYA patients. Future research should validate these findings in larger cohorts and explore the therapeutic potential of these markers.