The prognostic significance of Smad3, Smad4, Smad3 phosphoisoform expression in esophageal squamous cell carcinoma.

[esophageal squamous cell carcinoma]

Smad 3 functions as an integrator of diverse signaling , including transforming growth factor Î² signaling and the function of Smad 3 is complexly regulated by differential phosphorylation at various sites of Smad 3 . Despite the importance of Smad 3 and its various phosphoisoforms , their prognostic significance has rarely been studied . In this study , we demonstrated the prognostic significance of Smad 3 , its phosphoisoforms , and Smad 4 expression by immunohistochemistry in 126 esophageal squamous cell carcinomas . The phosphoisoforms of Smad 3 studied in this article included phosphorylation at C-terminal (pSmad 3 C )(Ser (423 /425 )) and phosphorylation at the linker region (pSmad 3 L )(Ser (213 )). High expression of Smad 3 was associated with shorter overall survival . Co -existence of high expression of pSmad 3 L (S 213 ) and low expression of pSmad 3 C (S 423 /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 pSmad 3 L (Ser (213 )) expression and low pSmad 3 C (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 Smad 3 on prognosis suggest the mode of action of Smad 3 might be logically determined by its phosphorylation pattern .

Diseases
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Diseases presenting "high psmad3" symptom

esophageal squamous cell carcinoma

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