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The Activation Status of the TGF-β Transducer Smad2 Is Associated with a Reduced Survival in Gastrointestinal Cancers: A Systematic Review and Meta-Analysis

Department of Diagnostics and Public Health, Section of Pathology, University of Verona, 37134 Verona, Italy
National Institute of Gastroenterology “S. de Bellis”, Research Hospital, Castellana Grotte, 70013 Bari, Italy
The Cambridge Centre for Sport and Exercise Sciences, Anglia Ruskin University, Cambridge CB1 1PT, UK
Primary Care Department, Azienda USL Toscana Sud Est, 58100 Grosseto, Italy
Department of Diagnostics, Section of Pathology, San Bortolo Hospital, 36100 Vicenza, Italy
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(15), 3831;
Received: 9 July 2019 / Revised: 31 July 2019 / Accepted: 1 August 2019 / Published: 5 August 2019
(This article belongs to the Special Issue TGF-Beta Super Family Signaling 2.0)
Aberrant function of Smad2, a crucial member of transforming growth factor beta (TGF-β) signaling, is associated with the development of malignancies, particularly in the gastrointestinal district. However, little is known about its possible prognostic role in such tumor types. With the first meta-analysis on this topic, we demonstrated that the lack of the activated form of Smad2 (phosphor-Smad2 or pSmad2), which was meant to be the C-terminally phosphorylated form, showed a statistically significant association with an increased risk of all-cause mortality in patients with gastrointestinal cancers (RR, 1.58; 95% CI, 1.05–2.37, p = 0.029, I2 = 84%), also after having adjusted for potential confounders (RR, 1.65; 95% CI, 1.24–2.18; p < 0.001; I2 = 4%). This finding highlights the importance of the TGF-β signaling in this type of cancer. In this line, further studies are needed to explore more in depth this important molecular pathway, focusing also on potential therapeutic strategies based on its effectors or molecular targets. View Full-Text
Keywords: Smad2; TGF-β; pSmad2; phosphorylation; signaling Smad2; TGF-β; pSmad2; phosphorylation; signaling
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Girolami, I.; Veronese, N.; Smith, L.; Caruso, M.G.; Reddavide, R.; Leandro, G.; Demurtas, J.; Nottegar, A. The Activation Status of the TGF-β Transducer Smad2 Is Associated with a Reduced Survival in Gastrointestinal Cancers: A Systematic Review and Meta-Analysis. Int. J. Mol. Sci. 2019, 20, 3831.

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