Background: The activator protein (AP)-2α is involved in a wide variety of biologic processes in tumor. However, little is known about the role of AP-2α in human papillary thyroid carcinoma (PTC).
Methods: The immunohistochemical method was used to detect AP-2α expression in 63 PTC cases. Western blotting was carried out to assess the change in expression of certain proteins. The bioinformatics analysis of 496 PTC samples comes from The Cancer Genome Atlas (TCGA). The Gene Set Enrichment Analysis (GSEA) was performed using TCGA data set. Cell ­transfection was used to induce related protein expression or to repress it by RNA interference procedures.
Results: Our results demonstrated that AP-2α expression was higher in tumor tissues than the corresponding adjacent nontumor tissues, the positive substances of AP-2α were observed mainly in the cytoplasm of PTC, and AP-2α was positively correlated with histologic type (P =0.026) of PTC patients. The high expression of AP-2α mRNA was associated significantly with tumor stages (P =0.011), histologic type (P =0.019), and independently predicted shorter overall survival (P =0.005) based on TCGA analysis. Patients with high AP-2α mRNA expression have shorter overall survival compared to those with low AP-2α mRNA expression, particularly in advanced tumor stages (III and IV) of PTC patients (P =0.011). Multivariate analysis suggested that AP-2α mRNA expression might be an independent prognostic indicator for the survival of patients with PTC (P =0.037). Moreover, the association between enhanced AP-2α expression and two pathways (notch signaling and focal adhesion) was revealed by GSEA, and then confirmed by cellular experiments.
Conclusion: Taken together, our findings suggest that AP-2α may be a potential prognostic molecular marker and therapeutic target for PTC patients.
Keywords: papillary thyroid carcinoma, AP-2α, prognosis, overall survival, notch signalling