Back to Search
Start Over
The prognostic significance of Smad3, Smad4, Smad3 phosphoisoform expression in esophageal squamous cell carcinoma.
- Source :
-
Medical oncology (Northwood, London, England) [Med Oncol] 2014 Nov; Vol. 31 (11), pp. 236. Date of Electronic Publication: 2014 Sep 30. - Publication Year :
- 2014
-
Abstract
- Smad3 functions as an integrator of diverse signaling, including transforming growth factor β signaling and the function of Smad3 is complexly regulated by differential phosphorylation at various sites of Smad3. Despite the importance of Smad3 and its various phosphoisoforms, their prognostic significance has rarely been studied. In this study, we demonstrated the prognostic significance of Smad3, its phosphoisoforms, and Smad4 expression by immunohistochemistry in 126 esophageal squamous cell carcinomas. The phosphoisoforms of Smad3 studied in this article included phosphorylation at C-terminal (pSmad3C)(Ser(423/425)) and phosphorylation at the linker region (pSmad3L)(Ser(213)). High expression of Smad3 was associated with shorter overall survival. Co-existence of high expression of pSmad3L(S213) and low expression of pSmad3C(S423/425) were associated with advanced N stage and an independent prognostic factor for overall [hazard ratio (HR) 2.03, 95 % confidence interval (CI) (1.10-3.75), p = 0.023] and disease-free survival [HR 2.41, 95 % CI (1.32-4.39), p = 0.004]. In conclusion, co-existence of high pSmad3L(Ser(213)) expression and low pSmad3C(Ser(423/425)) expression can be considered as immunohistochemical biomarkers for predicting prognosis as well as future therapeutic targets. In addition, our results of combinatory effect of differential phosphorylation of Smad3 on prognosis suggest the mode of action of Smad3 might be logically determined by its phosphorylation pattern.
- Subjects :
- Aged
Carcinoma, Squamous Cell mortality
Esophageal Neoplasms mortality
Esophageal Squamous Cell Carcinoma
Female
Humans
Male
Middle Aged
Prognosis
Protein Isoforms biosynthesis
Survival Rate trends
Biomarkers, Tumor biosynthesis
Carcinoma, Squamous Cell diagnosis
Carcinoma, Squamous Cell metabolism
Esophageal Neoplasms diagnosis
Esophageal Neoplasms metabolism
Gene Expression Regulation, Neoplastic
Smad3 Protein biosynthesis
Smad4 Protein biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1559-131X
- Volume :
- 31
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Medical oncology (Northwood, London, England)
- Publication Type :
- Academic Journal
- Accession number :
- 25267569
- Full Text :
- https://doi.org/10.1007/s12032-014-0236-9