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


CONCLUSIONS
These results provide convincing evidence for the first time that the JAK/STAT pathway may participate in the progress of ESCC.
Department of Chest Surgery, First Hospital of Huaian, Nanjing Medical University, Huaian 223300, China.
Zhenbing
Z
You
Dafu
D
Xu
Jian
J
Ji
Wei
W
Guo
Weiguo
W
Zhu
Jingdong
J
He
D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality* / Q000556:secondary; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D004947:Esophagus / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D053613:Janus Kinase 1 / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010766:Phosphorylation; D011379:Prognosis; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D015996:Survival Rate
D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C507904:JAK1 protein, human; D053613:Janus Kinase 1