Expression of Salt-Inducible Kinase 2 (SIK2) and its Correlation with Immune Cell Infiltration and Prognosis in Thyroid Papillary Carcinoma

Background Thyroid cancer(THCA) is the most common malignancy of the endocrine system, with papillary carcinoma being the most prevalent histopathological type. In recent years, its incidence has been continuously increasing, making it one of the fastest-growing malignancies in multiple countries. This study aims to investigate the relevance of Salt-Inducible Kinase 2 (SIK2) to this disease. Methods In this study,Reverse Transcription Quantitative Polymerase Chain Reaction(RT-qPCR),Enzyme-Linked Immunosorbent Assay (ELISA),Western Blotting (WB), Immunohistochemistry (IHC), and other experimental methods were employed to investigate the expression of SIK2 in thyroid cancer and adjacent tissues. WB, (Cell Counting Kit-8)CCK8 assay, Transwell assay, scratch test, and flow cytometry were used to analyze the activity of thyroid papillary carcinoma cells after SIK2 silencing. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis were conducted to guide further research directions. Immune infiltration was investigated using the Tumor Immune System Interaction Database (TISIDB), and prognosis-related analyses were performed using the Kaplan-Meier plotter and TIMRE2.0 databases. Results The protein level of SIK2 was significantly elevated in thyroid papillary carcinoma tissues compared to adjacent tissues. Silencing of SIK2 resulted in a significant reduction in the viability of thyroid papillary carcinoma cells, indicating its prognostic value. Additionally, using bioinformatics methods, the relationship between SIK2, immune cell infiltration, and prognosis in thyroid cancer was explored. Analysis using the TISIDB database showed a negative correlation between SIK2 expression and immune cell infiltration in thyroid cancer, suggesting a potential role of SIK2 dysregulation in tumor immune evasion. Kaplan-Meier plotter database analysis revealed different survival rates associated with different levels of immune cell infiltration, demonstrating clinical relevance. In patients with high SIK2 expression in thyroid cancer, decreased infiltration of B cells, CD8 + cells, macrophages, and regulatory T cells was associated with poorer prognosis, while increased infiltration of CD4 + T cells, eosinophils, mesenchymal stem cells, natural killer T cells, and Th1 cells was associated with better prognosis (all P < 0.05). TIMER2.0 analysis demonstrated that SIK2 was associated with better prognosis in males, stage 1, stage 2, and low tumor burden populations, and after 5 years of follow-up, the important outcome measure Overall Survival (OS) began to show statistical significance. Conclusion SIK2 is highly expressed in thyroid papillary carcinoma tissues and regulates cancer cell activity, likely through modulation of the surrounding immune microenvironment to influence disease progression.