Activation of STAT3 Signal Pathway Correlates with Twist and E-Cadherin Expression in Hepatocellular Carcinoma and Their Clinical Significance

• Published in: The Journal of surgical research 2012-05, Vol.174 (1), p.120-129
• Main Authors: Zhang, Chuan-Hai, M.D., Ph.D, Xu, Ge-Liang, B.S, Jia, Wei-Dong, M.D., Ph.D, Li, Jian-Sheng, B.S, Ma, Jin-Liang, M.S, Ren, Wei-Hua, Ph.D, Ge, Yong-Sheng, M.D., Ph.D, Yu, Ji-Hai, M.S, Liu, Wen-Bin, M.D, Wang, Wei, M.S
• Format: Article
• Language: English
• Subjects: Adult; Aged; Cadherins - analysis; Cadherins - physiology; Carcinoma, Hepatocellular - chemistry; Carcinoma, Hepatocellular - mortality; Carcinoma, Hepatocellular - pathology; E-cadherin; Female; hepatocellular carcinoma; Humans; Liver - chemistry; Liver Neoplasms - chemistry; Liver Neoplasms - mortality; Liver Neoplasms - pathology; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Nuclear Proteins - analysis; Nuclear Proteins - physiology; prognosis; signal transducer and activator of transcription 3; Signal Transduction - physiology; STAT3 Transcription Factor - analysis; STAT3 Transcription Factor - physiology; Surgery; Twist; Twist-Related Protein 1 - analysis; Twist-Related Protein 1 - physiology
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2010.10.030

Background To examine the expression of signal transducer and activator of transcription 3 (STAT3) and its activated form (p-STAT3), Twist, and E-cadherin in hepatocellular carcinoma (HCC), and explore their correlations with HCC progression and prognosis. Materials and Methods The expression profiles of STAT3, p-STAT3, Twist, and E-cadherin were assessed on 100 clinical HCC samples and 10 normal liver tissues by using an immunohistochemical staining method, and their correlations with clinicopathologic parameters and survival of HCC patients were statistically analyzed. Results The results demonstrated that the positive rate of STAT3, p-STAT3, and Twist in HCC was significantly higher than that in normal liver tissues; furthermore, 52% of HCC lesions showed reduced E-cadherin expression. Correlation analysis indicated that p-STAT3 was positively correlated with Twist expression, whereas Twist was negatively correlated with E-cadherin expression; p-STAT3, Twist, or E-cadherin expression was significantly associated with HCC invasion and metastasis. Survival analysis showed that HCC patients with p-STAT3, Twist positive expression, or reduced E-cadherin expression had a significantly shorter survival duration than those with p-STAT3, Twist negative expression, or those with normal E-cadherin expression. Multivariate analysis identified p-STAT3, Twist, or E-cadherin expression as an independent prognostic factor for overall survival of HCC patients after surgery. Conclusions By this study, we suggest that activated STAT3 signal may associate with Twist and E-cadherin expression and mediate HCC invasiveness and metastasis; abnormal p-STAT3/Twist/E-cadherin signal axis may predict poor prognosis of HCC patients.