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Meta-Analysis
. 2019 Aug 5;20(15):3831.
doi: 10.3390/ijms20153831.

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

Ilaria Girolami  1 , Nicola Veronese  2 , Lee Smith  3 , Maria G Caruso  2 , Rosa Reddavide  2 , Gioacchino Leandro  2 , Jacopo Demurtas  4 , Alessia Nottegar  5
Affiliations
Meta-Analysis

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

Ilaria Girolami et al. Int J Mol Sci. .

Abstract

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.

Keywords: Smad2; TGF-β; pSmad2; phosphorylation; signaling.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of the complex interactions involving TGF-β signaling and other important pathways in gastrointestinal tumors.
Figure 2
Figure 2
Forest-plot of relative risk of all-cause mortality: patients with pSmad2- have an increased risk of all-cause mortality, statistically significant (p = 0.029).
Figure 3
Figure 3
Forest-plot of adjusted risk of all-cause mortality: patients with pSmad2- have an increased risk of all-cause mortality, statistically significant after adjusting for potential confounders (p = 0.001).
See this image and copyright information in PMC

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