Abstract

BackgroundBoth phosphorylated signal transducer and activator of transcription 3(pStat-3) and integrin αvβ6 can play vital role in the development and progression of cancer. However, little is known about their expression correlation and clinical significance in gallbladder cancer(GBC).ObjectiveThe aim of our present study was to investigate the expression of pStat-3 and integrin αvβ6, two proteins’ correlation and their clinical significance in GBC tissues.ResultsThe expression of pStat-3 and integrin αvβ6 were both significantly associated with T stage, lymph node metastasis status, TNM stage (P=0.008, P=0.000, P=0.000 and P=0.036, P=0.001,P=0.000,respectively). IHC and Western blot showed their expressions in GBC tissues were higher than that in paraneoplastic tissues. Moderate positive correlation existed between the two proteins (r =0.349, P <0.001). The survival analysis by Kaplan-Meier and Cox regression model showed that GBC patients with pStat-3 or integrin αvβ6 positive expression had a significantly poorer 2-year survival rate (P = 0.002 and 0.000, the log-rank test, respectively), and either marker could act as unfavorable independent prognostic factors(RR=1.907, P=0.021 and RR=2.046, P=0.038).Materials and MethodsThe expression levels of pStat-3 and integrin αvβ6 were analyzed in GBC cancerous and paraneoplastic tissues of 97 cases via immunohistochemistry(IHC) and further validated by western blot method. Besides, SPSS software was used to observe their clinical significance as well as the two proteins’ correlation.ConclusionpStat-3 and integrin αvβ6 were indicators of tumor's progression and poor prognosis of patients with GBC. And the further study involving them may provide a helpful therapeutic target in prevention and treatment of GBC patients.

Highlights

  • Gallbladder cancer (GBC) is a highly aggressive malignant tumor of the biliary tract, which ranks fifth common among gastrointestinal cancers and accounts for 46% of biliary tract cancers in the United States [1]

  • The expression of pStat-3 and integrin αvβ6 were both significantly associated with T stage, lymph node metastasis status, TNM stage (P=0.008, P=0.000, P=0.000 and P=0.036, P=0.001,P=0.000,respectively)

  • The survival analysis by Kaplan-Meier and Cox regression model showed that GBC patients with pStat-3 or integrin αvβ6 positive expression had a significantly poorer 2-year survival rate (P = 0.002 and 0.000, the log-rank test, respectively), and either marker could act as unfavorable independent prognostic factors(RR=1.907, P=0.021 and relative risk (RR)=2.046, P=0.038)

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Summary

Introduction

Gallbladder cancer (GBC) is a highly aggressive malignant tumor of the biliary tract, which ranks fifth common among gastrointestinal cancers and accounts for 46% of biliary tract cancers in the United States [1]. The incidence rate of GBC is increasing worldwide, with a rather poor prognosis [2] Most of these patients are diagnosed at an advanced stage lacking chances of radical surgery [3], and only about 10% were detected at early stage [4]. Persistent Stat target gene activation can stimulate cell growth, angiogenesis, metastasis, and anti-apoptosis, thereby driving and sustaining tumorigenesis [9,10,11]. Both phosphorylated signal transducer and activator of transcription 3(pStat-3) and integrin αvβ can play vital role in the development and progression of cancer. Little is known about their expression correlation and clinical significance in gallbladder cancer(GBC)

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