Expression of Transforming Growth Factor β1, Smad3, and Phospho-Smad3 in Somatotropinomas and Their Relationship to Tumor Behavior

Abstract

Objective: To investigate the role of transforming growth factor β1 (TGF-β1), Smad3, and phospho-Smad3 (p-Smad3) in the invasion of somatotropinomas.

Methods: In total, 45 somatotropinomas were obtained from patients who underwent surgery for the first time between 2011 and 2015 at Beijing Tiantan Hospital. The expression of TGF-β1, Smad3, and p-Smad3 was examined by western blot, quantitative reverse transcription polymerase chain reaction, and immunohistochemistry in somatotropinomas, and factors correlated with tumor invasion were analyzed.

Results: A total of 13 invasive somatotropinomas and 32 noninvasive somatotropinomas were enrolled in the study. TGF-β1 protein (P < 0.01) and mRNA (P < 0.01) levels were significantly less in the invasive somatotropinomas than noninvasive somatotropinomas. There was no significant difference in Smad3 protein level or Smad3 mRNA level between invasive somatotropinomas and noninvasive somatotropinomas. However, the p-Smad3 protein level was significantly less in the invasive somatotropinomas than noninvasive somatotropinomas (P < 0.01). Univariate analysis demonstrated that TGF-β1 (P < 0.01) and p-Smad3 scores (P < 0.01) were associated with invasion. In multivariate analysis, p-Smad3 scores remained a significantly independent predictor of invasion (odds ratio 0.897, 95% confidence interval 0.834-0.964, P < 0.05).

Conclusions: Low expression of p-Smad3 is correlated with invasion of somatotropinomas.

Keywords: Invasion; Phospho-Smad3; Smad3; Somatotropinomas; TGF-β1.