DEPDC1 Promotes Thyroid Cancer Migration, Invasion, and Proliferation, and Correlates with Poor Prognosis

Background: We screened key genes involved in the dedifferentiation process of thyroid cancer by analyzing differentially expressed genes in anaplastic thyroid carcinoma (ATC) using Gene Expression Omnibus (GEO) database. Methods: We analyzed differentially expressed genes in ATC from GEO database and constructed a co-expression network using Weighted Gene Co-expression Network Analysis (WGCNA) . Cytoscape was used to calculate top ten key genes based on their gene scores. DEPDC1 was selected as interest gene for further validation, including examination of its prognostic relationship with thyroid cancer, correlation analysis with thyroid differentiation markers, immune cell infiltration, and tumor microenvironment. The impact of DEPDC1 on cancer cell migration, invasion, and proliferation was validated through downregulation and overexpression of DEPDC1 gene in thyroid cancer cell lines c643 and BCPAP. Results: We identified top 10 key genes in ATC: AURKA, TPX2, RACGAP1, MELK, DLGAP5, DEPDC1, KIF2C, NCAPG, CCNB1, and PBK. DEPDC1 showed a strong correlation with the prognosis of thyroid cancer. The odds ratio (OR) for overall survival was 3.5 (P=0.016) in individuals with high DEPDC1 expression, and the OR for disease-free survival was 2.6 (P=0.003). Additionally, the analysis revealed a significant negative correlation between the expression of DEPDC1 and thyroid differentiation markers. Gene Ontology enrichment analysis demonstrated that DEPDC1 co-expressed genes were enriched in cellular processes, cell cycle pathways, and dynamic protein groups. Matrix and immune scoring indicated tumor microenvironment and immune scores were associated with DEPDC1 expression. TIMER2.0 online analysis revealed a strong correlation between DEPDC1 expression and immune cell infiltration in papillary thyroid carcinoma. After downregulation of DEPDC1 expression, the invasion, migration, and proliferation abilities of tumor cells were significantly reduced. Conversely, overexpression of DEPDC1 exhibited the opposite effect. Conclusion: DEPDC1, a newly identified dedifferentiation gene in thyroid cancer, inversely correlated with the degree of differentiation. High expression of DEPDC1 promotes cancer progression and leads to poor prognosis in thyroid cancer.