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Tumor Biology

, Volume 33, Issue 4, pp 1005–1014 | Cite as

Prognostic significance of transforming growth factor beta (TGF-β) signaling axis molecules and E-cadherin in colorectal cancer

  • Pavlos Lampropoulos
  • Adamantia Zizi-Sermpetzoglou
  • Spyros Rizos
  • Alkiviadis Kostakis
  • Nikolaos Nikiteas
  • Athanasios G. Papavassiliou
Research Article

Abstract

The transforming growth factor beta (TGF-β) signaling pathway has been considered both a tumor suppressor and a cancer promoter. Additionally, downregulation of cell adhesion molecules such as E-cadherin plays an important role in the metastatic potential of colorectal cancer (CRC). The aim of the present study was to evaluate TGF-β, TGF-β type I receptor (TGF-βR1), TGF-β type II receptor (TGF-βR2), Smad4, pSmad2/3, and E-cadherin expression in colorectal carcinoma and to correlate the obtained data with other standard prognostic parameters, such as disease stage, metastases, and patient survival. TGF-β, TGF-βR1, TGF-βR2, Smad4, pSmad2/3, and E-cadherin expression was evaluated immunohistochemically in 195 unrelated CRC specimens and the results subjected to various statistical analyses. TGF-β was expressed in 71.28%, TGF-βR1 in 61.0%, TGF-βR2 in 54.4%, Smad4 in 61.5%, pSmad2/3 in 71.3%, and E-cadherin in 50.26% of the colorectal carcinoma samples tested. The correlation of immunoexpression with the clinicopathological parameters of CRC revealed that the high expression of TGF-β and low expression of TGF-βR1, TGF-βR2, Smad4, pSmad2/3, and E-cadherin were correlated with tumor–node–metastasis (TNM) stage of disease. High TGF-β expression and low TGF-βR1, TGF-βR2, Smad4, and pSmad2/3 expression were also correlated with lymph node metastasis. The Kaplan–Meier survival curves demonstrated a clear association of cancer-specific overall survival with high TGF-β, as well as low TGF-βR1, TGF-βR2, Smad4, pSmad2/3, and E-cadherin expression. Our results suggest that TGF-β, TGF-βR1, TGF-βR2, Smad4, pSmad2/3, and E-cadherin are closely related to TNM stage of CRC. Moreover, TGF-β, TGF-βR2, Smad4, pSmad2/3, and E-cadherin emerge as valuable independent biomarkers of prognosis in CRC patients.

Keywords

TGF-β signaling Smads E-cadherin Colorectal cancer (CRC) 

Notes

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2012

Authors and Affiliations

  • Pavlos Lampropoulos
    • 1
  • Adamantia Zizi-Sermpetzoglou
    • 2
  • Spyros Rizos
    • 1
  • Alkiviadis Kostakis
    • 3
  • Nikolaos Nikiteas
    • 3
  • Athanasios G. Papavassiliou
    • 4
  1. 1.First Department of Surgery“Tzaneio” General HospitalAthensGreece
  2. 2.Department of Pathology“Tzaneio” General HospitalAthensGreece
  3. 3.Second Department of Propaedeutic SurgeryUniversity of Athens Medical SchoolAthensGreece
  4. 4.Department of Biological ChemistryUniversity of Athens Medical SchoolAthensGreece

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