Molecular And Clinical Significance of PDGFR Family in Papillary Thyroid Cancer: A Systematic Review

Abstract

Objective: Papillary thyroid cancer (PTC) is the most prevalent endocrine cancer. Activation of platelet-derived growth factor receptors (PDGFRs) is involved in the development of thyroid cancers. This systematic review aims to evaluate the molecular and clinical significance of PDGFRs in PTC. Method: A comprehensive literature search was performed in PubMed, Scopus, and Web of Science databases up to August 2024, focusing on studies evaluating PDGFRα/β variants, expression levels, and clinical outcomes in PTC. Eligible studies were selected according to PRISMA guideline. Studies including unknown histology, insufficient data, case reports, non-human experiments, and review article were excluded. The REMARK criteria were applied for quality assessment of the included studies. Results: A total of twelve studies were included. Genetic alterations in the promoter of PDGFRα (rs6554162 and rs1800812) showed a significant association with increased risk of PTC, while synonymous variants were more frequently detected in benign tumors. In contrast, noncoding variants in PDGFRβ showed no association with PTC. Overexpression of PDGFRα was significantly associated with lymph node metastasis, larger tumor size, poorer disease-free survival (DFS) with some inconsistency and poor response to radioactive iodine therapy. Findings on PDGFRβ expression were inconsistent. However, one study reported its upregulation in metastatic PTC and its association with shorter overall survival in patients with BRAFV600E. Conclusion: PDGFRα may serve as a potential biomarker associated with aggressive tumor behavior and treatment failure in people with PTC. Further experimental studies are needed to validate the results. Targeting PDGFRα may represent a therapeutic approach, but evidence is still insufficient.

Keywords: PDGFRα/β, Thyroid cancer, Biomarker, PDGFR expression, Genetic variation