Pigment epithelium-derived factor has a role in the progression of papillary thyroid carcinoma by affecting the HIF1α-VEGF signaling pathway

色素上皮衍生因子通过影响HIF1α-VEGF信号通路在乳头状甲状腺癌的进展中发挥作用。

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Abstract

The progression mechanism of papillary thyroid carcinoma (PTC) remains largely unknown. Accumulating evidence has suggested that various targets of pigment epithelium-derived factor (PEDF) are able to inhibit cancer progression. The aim of the present study was to examine PEDF expression in PTC patients and to investigate its relationship with aggressive clinicopathological features, as well as to explore whether PEDF affects the progression of PTC via the hypoxia-inducible factor 1α (HIF1α)-vascular endothelial growth factor (VEGF) pathway. A total of 271 patients with PTC, including 24 men and 247 women, were enrolled in the present study. Relevant patient data, including demographic features, preoperative clinical features and pathological features, were collected for analysis. The protein expression levels of PEDF in PTC tissues were detected using immunohistochemical staining, and the mRNA expression levels of PEDF, VEGF and HIF1α in 15 PTC tissues with lymph node metastasis (LNM) and 10 tissues without LNM were detected using reverse transcription-quantitative polymerase chain reaction. Immunohistochemical staining with an anti-PEDF antibody detected PEDF expression in 74.5% of the PTC tissues. PEDF expression levels were significantly correlated with LNM, extrathyroid invasion, a high TNM stage, the presence of the BRAF(V600E) mutation and tumor size. PEDF mRNA expression levels were significantly decreased in PTC tissues with LNM, as compared with PTC tissues without LNM, while the mRNA expression levels of HIF1α and VEGF were markedly increased in PTC tissues with LNM. Taken together, the results of the present study suggested that PEDF plays a role in the progression of PTC, and that PEDF may exert an anti-angiogenesis role by affecting the HIF1α-VEGF pathway, eventually inhibiting the metastasis of PTC.

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