Alkaline phosphatase (ALPL) as a diagnostic and prognostic biomarker linked to immune response in thyroid cancer.

BACKGROUND

Thyroid cancer (THCA) is a rapidly increasing endocrine malignancy. This study aims to explore alkaline phosphatase (ALPL) as a potential prognostic biomarker and therapeutic target, focusing on its role in tumor progression and immune infiltration.

METHODS

We utilized RNA sequencing (RNA-Seq) data from The Cancer Genome Atlas (TCGA) to investigate the role of ALPL in THCA. Comprehensive analyses included differential gene expression, survival outcomes, immune cell infiltration, and RNA methylation correlations. Functional assays such as cell counting kit-8, colony formation, Transwell migration/invasion, 5-ethynyl-2'-deoxyuridine (EdU) staining, and flow cytometry were conducted to evaluate the effects of ALPL knockdown in THCA cell lines. At the same time, we constructed a nomogram.

RESULTS

Our study identified ALPL as a key biomarker in THCA through TCGA analysis. The expression of ALPL was significantly elevated in tumor tissues and correlated with worse overall survival (OS). Moreover, we verified the expression of ALPL in patients with THCA. Functional assays showed that ALPL knockdown inhibited proliferation by 40-50%, reduced migration and invasion by 35-45%, and diminished clonogenic potential. Flow cytometry revealed a 2-fold increase in apoptosis. ALPL was also linked to immune infiltration, RNA methylation, and vascular endothelial growth factor (VEGF)/calcium signaling pathways, highlighting its role in tumor progression and potential as a therapeutic target. The nomogram that we constructed showed high value in predicting prognosis.

CONCLUSIONS

ALPL is a key biomarker in THCA, driving tumor progression and poor outcomes through its roles in proliferation, invasion, and immune modulation. These findings support its potential as a diagnostic and prognostic marker.