JAK/STAT signal pathway activation promotes progression and survival of human oesophageal squamous cell carcinoma

Abstract

Objective: Inappropriate activation of JAK/STAT pathway occurs with high frequency in human cancers and is associated with cancer cell survival and proliferation. However, its role in oesophageal squamous cell carcinoma (ESCC) is unknown.

Methods: By immunohistochemistry, we analysed the expression of two components of this pathway, phosphorylated JAK-1 (pJAK-1) and phosphorylated STAT-3 (pSTAT-3), in 100 ESCC tumours and paired non-neoplastic oesophageal epithelia. Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of patients.

Results: We found that pJAK-1 and pSTAT-3 expression was not detectable in normal oesophageal squamous cells. Primary ESCC with pJAK-1-positive and pSTAT-3-positive expression was detected in the cancer cell nests of 78 and 72 cases, respectively. In addition, the Pearson's correlation coefficient between pJAK-1 and pSTAT-3 expression was 0.806 (p<0.001). Moreover, pJAK-1 and pSTAT-3 expression was correlated with N stage (lymph node metastasis, both p=0.01), pTNM stage (p=0.008 and 0.009, respectively) and metastatic status (both p=0.01). Furthermore, pJAK-1 and pSTAT-3 expression was associated with shorter overall survival (both p<0.001) and shorter disease-free survival (p=0.005 and 0.006, respectively). By multivariate analysis, TNM clinical classification (T, p<0.001; N, p=0.002; M, p=0.02), pJAK-1 (p=0.002) and pSTAT-3 (p=0.003) were independent prognosis predictors of ESCC.

Conclusion: These results provide convincing evidence for the first time that the JAK/STAT pathway may participate in the progress of ESCC.