Expression and significance of signal transducers and activators of transcription 3 pathway genes in cholangiocarcinoma
Zhaojun HUANG
;
Qiang HUANG
;
Chenhai LIU
;
Fang XIE
;
Chenglin ZHU
Chinese Journal of Digestive Surgery.2014;13(12):971-976. doi:10.3760/cma.j.issn.1673-9752.2014.12.014
Objective To investigate the expression of STAT3 signaling pathway genes including Survivin and COX-2 in cholangiocarcinoma,as well as the relationship between expression of these genes and prognosis of patients with cholangiocarcinoma.Methods The tumor and normal tissue samples were respectively collected from 43 patients with cholangiocarcinoma and 12 patients with intra-and extrahepatic bile duct stones or hepatic duct injury in the Affiliated Provincial Hospital of Anhui Medical University from September 2007 to July 2012.The expression of STAT3,phosphorylated-STAT3 (p-STAT3),Survivin and COX-2 were examined using immunohistochemistry,and the relationship between the expression of these genes and the clinical pathological features and prognosis of patients with cholangiocarcinoma was analyzed.Patients were followed-up through outpatient examination and telephone interview until March 2014.Categorical data were analyzed using the chi-square test.Correlation analysis was done by Spearman's method.The survival curve was generated using the Kaplan-Meier method,and the survival analysis was conducted using the log-rank test.Results The positive expression rates of STAT3,p-STAT3,Survivin and COX-2 in the tumor samples were 69.8％ (30/43),65.1％ (28/43),72.1％ (31/43),79.1％ (34/43),respectively,which were compared with 41.7％ (5/12),8.3％ (1/12),16.7％ (2/12) and 41.7％ (5/12) in the normal tissue samples,showing a significant difference for the last 3 indexes (x2=12.136,9.811,4.679,P ＜ 0.05).Overexpression of p-STAT3,Survivin and COX-2 protein was correlated with lymph node metastasis (x2 =14.700,5.959,4.075,P ＜ 0.05).Overexpression of p-STAT3 was also related to neural invasion (x2=10.384,P ＜ 0.05).Expression of Survival and COX-2 protein was not associated with lymph invasion (x2=2.718,3.024,P ＞ 0.05).Expression of p-STAT3,Survivin and COX-2 was however not associated with gender,age and tumor location,differentiation and diameter (x2=0.148,0.720,1.835,1.040,0.236 ; 0.001,0.009,0.029,1.863,0.197 ; 0.433,0.686,0.002,2.974,0.029,P ＞ 0.05).Expression of Survivin and COX-2 protein was positively correlated to p-STAT3 protein (r =0.524,0.583,P ＜ 0.05).All the 43 patients were followed up for 6-60 months.Among the 17 patients with hilar cholangiocarcinoma,the median survival time was 7,9,9 months for patients with positive expression of p-STAT3,Survivin and COX-2 protein,compared with 18,11 and 11 months for patients with negative expression of these proteins.The survival rates of the patients with positive and negative expression of p-STAT3 protein were 33.3％ and 68.6％,respectively,with a statistical significance for p-STAT3 protein (x2=12.916,P ＜ 0.05).Of the remaining 26 patients with common bile duct carcinoma,the median survival time was 9,10 and 9 months for patients with positive expression of p-STAT3,Survivin and COX-2 protein,compared with 20,20 and 20 months for patients with negative expression of these proteins.The survival rates of the patients with positive expression of p-STAT3,Survivin and COX-2 protein were 20.8％,9.4％ and 8.5％,which were lower than 37.5％,37.5％ and 50.0％ of patients with the negative expression of these proteins,with a statically significance for all the 3 proteins (x2=12.787,6.245,11.161,P ＜ 0.05).Conclusions The p-STAT3,Survivin,COX-2 proteins are highly expressed in the cholangiocarcinoma and the expression levels of these proteins are positively correlated.The survivin and COX-2 may be the downstream genes of STAT signaling pathway,which are involved in the progression and prognosis of cholangiocarcinoma.
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