Abstract
OBJECTIVE: The incidence of thyroid cancer (TC) is increasing in China, largely due to overdiagnosis from widespread screening and improved ultrasound technology. Identifying precise TC biomarkers is crucial for accurate diagnosis and effective treatment. METHODS: TC patient data were obtained from TCGA. DEGs were analyzed using DESeq2, and WGCNA identified gene modules associated with TC. Machine learning algorithms (XGBoost, LASSO, RF) identified key biomarkers, with ROC and AUC > 0.95 indicating strong diagnostic performance. Immune cell infiltration and biomarker correlation were analyzed using CIBERSORT. RESULTS: Four key genes (P4HA2, TFF3, RPS6KA5, EYA1) were found as potential biomarkers. High P4HA2 expression was associated with suppressed anti-tumor immune responses and promoted disease progression. In vitro studies showed that P4HA2 upregulation increased TC cell growth and migration, while its suppression reduced these activities. CONCLUSION: Through bioinformatics and experimental validation, we identified P4HA2 as a key potential thyroid cancer biomarker. This finding provides new molecular targets for diagnosis and treatment. P4HA2 has the potential to be a diagnostic or therapeutic target, which could have significant implications for improving clinical outcomes in thyroid cancer patients.