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In this study, we performed whole transcriptomic sequencing on 113 PTC cases, including 70 high\u2010risk and 43 low\u2010risk Chinese patients. Comparative transcriptional profiling analysis revealed two functionally distinct patterns of gene dysregulation between the risk subtypes. Low\u2010risk PTCs showed significant upregulation of immune\u2010related genes and increased immune cell infiltration, whereas high\u2010risk PTCs presented extensive alterations in gene expression and activation of oncogenic signaling pathways. Additionally, we developed a 31\u2010gene transcriptomic signature (PTCrisk) for differentiating high\u2010risk from low\u2010risk PTCs, which was validated across both in\u2010house and external multicenter cohorts. PTCrisk scores were positively correlated with key clinicopathological features, including tumor size, lymph node metastasis, TNM stage, and <jats:italic>BRAF<\/jats:italic> mutation status. Overall, our study provides further molecular insights into PTC risk stratification and may contribute to the development of personalized therapeutic strategies for PTC patients.<\/jats:p>","DOI":"10.1002\/2056-4538.70022","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T12:06:13Z","timestamp":1741694773000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Comprehensive transcriptomic profiling reveals molecular characteristics and biomarkers associated with risk stratification in papillary thyroid carcinoma"],"prefix":"10.1002","volume":"11","author":[{"given":"Congcong","family":"Yan","sequence":"first","affiliation":[{"name":"School of Biomedical Engineering Wenzhou Medical University  Wenzhou PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery The First 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