Clinicopathological significance of expression of JAB 1 and Smad 4 in human esophageal squamous cell carcinoma

INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE(2016)

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Abstract
c-Jun activation domain-binding protein-1 (JAB1) and mothers against decapentaplegic homolog (Smad) 4 are abnormally expressed in many malignant tumors, and involved in occurring and progressing of malignant tumors. The aim of this study is to investigate the expression of JAB1 and Smad4 in human esophageal squamous cell carcinoma (ESCC) and explore their clinical and pathological significance. The expression of JAB1 and Smad4 protein were detected in 187 cases of human ESCC and 23 cases of tumor-adjacent tissues by immunohistochemical method. Our results demonstrate that the positive rate of JAB1 was 65.2% in human ESCC which was higher than that in tumor-adjacent tissues (17.4%), <0.001. High levels of JAB1 protein were significantly related to differentiation, TNM stage, lymphatic metastasis and depth of invasion (P = 0.011, P = 0.001, P<0.001 and P = 0.002, respectively). The positive rate of Smad4 was 43.3% in ESCC tissues, which was lower than that in tumor-adjacent tissues (78.3%), P = 0.002. Low levels of Smad4 protein were significantly related to tumor differentiation, TNM stage, lymphatic metastasis and depth of invasion (P = 0.039, P = 0.003, P<0.001 and P<0.001, respectively). JAB1 protein was inversely correlated with Smad4 protein (r = -0.518, P<0.001). Patients with higher JAB1 or lower Smad4 expression had shorter overall survival time, while patients with lower JAB1 or higher Smad4 expression had better survival time. Multivariate logistic regression analysis showed that TNM stage, lymphatic metastasis as well as the JAB1 expression were negatively correlated with disease free survival (P = 0.018, P = 0.019 and P = 0.035, respectively) and overall survival of ESCC (P<0.001, P = 0.043 and P = 0.012, respectively), and Smad4 expression were positively correlated with disease free survival (0.033) and overall survival of ESCC (P = 0.023). In conclusion, expression of JAB1 and Smad4 are markedly related with differentiation, TNM stage, lymphatic metastasis and depth of invasion of ESCC. JAB1 is inversely related with the expression of Smad4. To detect JAB1 and Smad4 may be helpful to evaluate prognosis and infiltrative capability of ESCC.
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Key words
Esophageal squamous cell carcinoma, immunohistochemistry, JAB1, Smad4, invasion, survival
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