A Meta-analysis Of Phospho-STAT3 Expression And Clinical Significance In Patientswith Colorectal Cancer

Background: Phosphorylated signal transducer and activator of transcription 3(p-STAT3)promote tumor cell proliferation and resistance to apoptosis.However,the exact role of p-STAT3 in colorectal cancer remains controversial.Objective: We performed a meta-analysis evaluating p-STAT3 activation in colorectal cancers and its association with clinicopathological variables and prognosis.Methods: Eligible studies were retrieved by systematically searching the Pub Med,Web of Science,CBM,CNKI,VIP,and Wanfang databases.We screened the reports for eligibility against the inclusion and exclusion criteria and then extracted data from the shortlisted studies using pre-specified forms.The methodological quality of included study was also assessed using NOS criteria.Odds ratio(OR)and hazard ratio(HR)[and their corresponding 95% confidence intervals(CIs)] were considered as a measure of evaluating the association in meta-analysis.Influence,sensitivity,subgroup and meta-regression analyses were used to examine whether any had an impact on the results of this meta-analysis.Publication bias was assessed with funnel plot and Egger's test.Statistical computations were performed with STATA 11.0 and Rev Man 5.1softwares.Results: Thirteen studies including 1724 patients which evaluated theResults: Thirteen studies including 1724 patients which evaluated the p-STAT3 expression in colorectal cancers were included.The study quality was moderate.The rate of p-STAT3 positive expression in colorectal patients was significantly higher than patients in control groups(OR14.34,95% CI 3.43-59.89,P < 0.001).No significant differences were found between p-STAT3 positivity rates and sex(OR 1.02,95% CI 0.80-1.30,P= 0.86),age(OR 1.30,95% CI 0.99-1.71,P = 0.06),and metastasis(OR1.89,95% CI 0.44-8.12,P = 0.39).The p-STAT3 immunoreactivity significantly correlated with poor differentiation of tumor(OR 2.25,95% CI 1.26-4.01,P = 0.006),tumor size(OR 3.59,95% CI 1.17-10.98,P = 0.02),the depth grading of tumor invasion(OR 5.12,95% CI 2.52-10.41,P < 0.001),lymphatic invasion(OR 3.95,95% CI 2.43-6.43,P < 0.001),and TNM' stage(OR 2.41,95% CI 1.09-5.32,P = 0.03).Expression of p-STAT3 was a marker of poor prognosis in overall survival(HR 1.68,95% CI1.11-2.53,P = 0.01).The subsequent influence,sensitivity,subgroup and meta-regression analyses did not identify factors that affect the role of p-STAT3 in colorectal patients,including publication years,country,sample,mean age,male,the proportion of colon cancer,treatment,follow-up time,various cut-off values of p-STAT3 positive expression,anti-p-STAT3 antibody,cases of p-STAT3 positive expression,and study quality score(P > 0.05).No funnel plot asymmetry was found.The Egger test then was adopted to provide statistical evidence of funnel plot symmetry.The results did not suggest any evidence of publication bias(P > 0.05).Conclusion: Our meta-analysis indicates that the increased p-STAT3 expression may be not only predict poor prognosis,but also be associated with worse tumor differentiation,tumor size,invasion depth,lymph node metastasis and TNM stages in patients with colorectal cancer.Future prospective studies with good design and adequate follow up are needed to confirm the value of p-STAT3 in colorectal cancers.