Genomic Characterization of Papillary Thyroid Carcinoma: Age Differences in Tumor Aggressiveness and Immune Infiltration

Adolescents and Young Adults (AYA) with papillary thyroid carcinoma (PTC) tend to exhibit more aggressive metastatic features compared to Adults (AD), despite low overall tumor proliferation. This study statistically analyzed clinical data from 501 PTC patients in The Cancer Genome Atlas (TCGA), categorized as Adolescents and Young Adults (AYA) and Adults (AD), to uncover differential clinical features between the two age groups.An independent cohort of 13 patients (7 AYA, 6 AD) was used to screen for differentially expressed genes (DEGs) through RNA sequencing. Functional enrichment and topology analyses identified core molecules associated with the heightened aggressiveness of age-related tumors, which were subsequently validated using immunohistochemistry (IHC). Among the 239 core DEGs identified between AYA and AD PTC, key genes such as CXCR4, OPCML, and S100A2 were upregulated in AYA, while ATP1A3, CHL1, HLA-DRA, and IL-1 Beta were downregulated. These genes play a crucial role in tumor invasion and are linked to immune cell infiltration. These findings suggest that integrating age-specific molecular markers into clinical management could enhance diagnostic accuracy and enable personalized treatment strategies for AYA patients, with further research needed to validate these results in larger cohorts and explore their therapeutic potential.