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, Nicola Veronese, Lee Smith, Maria G Caruso, Rosa Reddavide, Gioacchino Leandro, Jacopo Demurtas, Alessia Nottegar

Research output: Contribution to journalReview article

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.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalInternational Journal of Molecular Sciences
Volume20
Issue number15
DOIs
Publication statusPublished - Aug 5 2019

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beta factor
Gastrointestinal Neoplasms
Transducers
Transforming Growth Factor beta
Meta-Analysis
transducers
cancer
Chemical activation
activation
effectors
Survival
mortality
Phosphors
phosphors
Tumors
Neoplasms
tumors
Association reactions
causes
Mortality

Cite this

The Activation Status of the TGF-β Transducer Smad2 Is Associated with a Reduced Survival in Gastrointestinal Cancers : A Systematic Review and Meta-Analysis. / Girolami, Ilaria; Veronese, Nicola; Smith, Lee; Caruso, Maria G; Reddavide, Rosa; Leandro, Gioacchino; Demurtas, Jacopo; Nottegar, Alessia.

In: International Journal of Molecular Sciences, Vol. 20, No. 15, 05.08.2019, p. 1-11.

Research output: Contribution to journalReview article

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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.",
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T1 - The Activation Status of the TGF-β Transducer Smad2 Is Associated with a Reduced Survival in Gastrointestinal Cancers

T2 - A Systematic Review and Meta-Analysis

AU - Girolami, Ilaria

AU - Veronese, Nicola

AU - Smith, Lee

AU - Caruso, Maria G

AU - Reddavide, Rosa

AU - Leandro, Gioacchino

AU - Demurtas, Jacopo

AU - Nottegar, Alessia

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AB - 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.

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