Serum Follistatin Is Increased in Thyroid Cancer and Is Associated With Adverse Tumor Characteristics in Humans

Abstract

Context: Obesity and classical growth factors are associated with thyroid cancer (TC). However, less is known regarding novel hormones such as follistatins and activins. We hypothesized that serum follistatin but not activins would be increased in TC.

Objective: This work aimed to assess circulating levels of follistatins, activins, and growth factors in patients with a history of TC vs patients with nonmalignant thyroid diseases.

Methods: A hospital-based, unmatched case-control study was conducted with 170 thyroidectomized patients due to well-differentiated TC and 106 thyroidectomized patients without history of malignancy. Anthropometric, biochemical, and histological parameters were recorded. Serum samples were collected in the steady state 45 days after surgery. Multivariate models were used to adjust for baseline differences of the unmatched variables. Serum levels of follistatin (FST), follistatin like-3, activin A, activin B, bioactive insulin-like growth factor-1, and stanniocalcin-2 were assayed with novel, highly specific ELISA kits.

Results: In unmatched univariate models, TC patients had higher FST serum levels compared to cancer-free individuals, independently of histological subtype. In multivariate models adjusting for covariates, individuals in the highest tertile of FST levels were associated with an increased risk for the presence of any type of TC or specific histological subtypes, including papillary, follicular and Hürthle-cell carcinoma, and medullary TC. Higher postoperative FST concentrations were found in patients with vascular invasion and distant metastases and associated with TNM staging at diagnosis.

Conclusion: FST serum levels are increased in TC patients and correlate with advanced tumor aggressiveness. Future longitudinal studies are needed to confirm and extend our observations.

Keywords: growth factors; obesity; thyroid cancer; tumor biomarker.