title: Prognostic significance of transforming growth factor beta (TGF-β) signaling axis molecules and E-cadherin in colorectal cancer.
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.
authors.affiliation: First Department of Surgery, Tzaneio General Hospital, Athens, Greece. pav.lampropoulos@gmail.com
authors.forename: Pavlos
authors.initials: P
authors.lastname: Lampropoulos
authors.forename: Adamantia
authors.initials: A
authors.lastname: Zizi-Sermpetzoglou
authors.forename: Spyros
authors.initials: S
authors.lastname: Rizos
authors.forename: Alkiviadis
authors.initials: A
authors.lastname: Kostakis
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Nikiteas
authors.forename: Athanasios G
authors.initials: AG
authors.lastname: Papavassiliou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000706:statistics & numerical data; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010766:Phosphorylation; D011379:Prognosis; D016016:Proportional Hazards Models; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D051901:Smad4 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D018125:Receptors, Transforming Growth Factor beta; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; C497796:SMAD4 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D051901:Smad4 Protein; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II