Effect of thyroidectomy on circulating angiogenic cytokines in papillary thyroid carcinoma and benign goiter: Potential for new biomarkers?

Abstract

Background: Circulating angiogenic factors have been associated with clinical outcomes of papillary thyroid carcinoma, although they may also be released in the context of benign multinodular goiter. We sought to investigate the effect of thyroidectomy on the activity and importance of multiple circulating angiogenic factors in papillary thyroid carcinoma and benign multinodular goiter. Methods: Between May 2015 and December 2016, patients scheduled for total thyroidectomy for papillary thyroid carcinoma or benign multinodular goiter were offered to enroll in this study. Serum levels of angiopoietin-2, fibroblast growth factor-2, hepatocyte growth factor, platelet-derived growth factor-BB, placenta growth factor, heparin-binding epidermal growth factor, and vascular endothelial growth factor-A and-C were collected preoperatively and 2 weeks postsurgery. These levels were measured by enzyme-linked immunosorbent assay and compared with those of 35 healthy control subjects. Results: Sixty patients with a median age of 52 years, 37 of whom were females, were included: 36 had papillary thyroid carcinoma, and 24 had benign multinodular goiter. In both benign multinodular goiter and papillary thyroid carcinoma, preoperative, circulating angiogenic factors levels were increased with respect to controls (P < .0001), and a decrease after total thyroidectomy was observed in the levels of angiopoietin-2 (P < .0001), fibroblast growth factor-2 (P < .0001), hepatocyte growth factor (P < .001), and heparin-binding epidermal growth factor (P < .01 each). Only patients with papillary thyroid carcinomas, however, showed decrease in the postoperative levels of platelet-derived growth factor-BB and vascular endothelial growth factor-A (P ¼ .001 each). Conclusion: Results from this study raise the potential for vascular endothelial growth factor-A and platelet-derived growth factor-BB to be used as biomarkers of the effectiveness of treatment of papillary thyroid carcinoma. These results warrant further investigation and may have potential prognostic implications.

Decreased circulating levels of angiopoietin – 1 (Ang-1) are associated with the presence of benign or malignant thyroid disease.

“…It should be noted that 40% of the PTC cohort had stage III or IV disease. Ria et al reported signi cantly greater levels of VEGF-A in PTC and MNG patients as compared to healthy subjects [17]. Our results did not demonstrate differences between the studied groups.…”

“…Niedzwiecki et al did not observe overall differences but in subgroup analysis levels of Ang-2 were signi cantly lower in PTC patients [14]. In a recent study with similar exclusion criteria as our own study design, levels of Ang-2 were elevated in PTC and benign thyroid disease compared to healthy controls [17]. Postoperative levels also exhibited a marked decline in both groups.…”

Role of Basic Fibroblast Growth Factor in Cancer: Biological Activity, Targeted Therapies, and Prognostic Value

“…Recent scientific evidence has shown that angiogenic factor profiling can be useful in the deepening of tumor biological tools and highly useful in strengthening therapeutic strategies for papillary thyroid carcinoma (PTC) [ 158 ]. PTC patients revealed substantial bFGF levels when compared to healthy controls; however, a total thyroidectomy surgical procedure resulted in the successful decreasing of bFGF overexpression [ 158 ]. Moreover, miRNAs such as miR-27b-3p and miR-195 were probed in the context of thyroid cancer [ 159 , 160 ].…”

Prognostic and Therapeutic Role of Angiogenic Microenvironment in Thyroid Cancer

“…Natural inhibitors of MMPs are the tissue inhibitors of metalloproteinases (TIMPs), produced and released in the tumor microenvironment [ 93 ]. Published data from our group indicate that the MMPs’ proangiogenic and pro-tumoral activities are related to the balance of MMPs and TIMPS in the microenvironment, and that the switch toward an invasive phenotype is mainly due to increased MMP production and release, and not to the reduction of TIMPs ( Figure 1 ) [ 94 , 95 ].…”

“…A possible application for this aim is the assay of miRNA in exosomes, especially miR-21-5p [ 52 , 125 ], which is a decisive proangiogenic factor produced by thyroid cancer cells. VEGF-A and PDGF-BB have been recently indicated as potential circulating biomarkers of PTC treatment [ 94 ].…”