| Objective: Cholangiocarcinoma(CCA)has a high degree of malignancy and is a heterogeneous tumor formed by the malignant transformation of bile duct cells along the biliary tract,which is divided into intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma anatomically.In recent years,the incidence has been increasing year by year,accounting for 7-10% of hepatobiliary malignant tumors.Inflammatory changes in the bile duct wall caused by some benign lesions are difficult to be pathologically differentiated from canceration.Besides,CCA lacks specific tumor markers.Most of the patients are diagnosed with late stage.Only 20% of patients can be treated with radical surgical resection.The prognosis of patients with cholangiocarcinoma is poor.Therefore,further studies are needed on the prognostic markers and new treatments.Among them,the programmed cell death-ligand 1(PD-L1),also known as CD274 or B7-H1,is one of the ligands of the programmed cell death(PD-1),which plays an important role in the immune escape of malignant tumors.Related studies have shown that the overexpression of PD-L1 is associated with the clinicopathological features and prognosis of various malignant tumors,and has the potential to predict the efficacy of immunocheckpoint inhibitors.However,there are few studies on cholangiocarcinoma.Moreover the conclusions are controversial.Therefore,the Meta-analysis was conducted to investigate the expression of PD-L1 in CCA and its clinical value.Methods: By searching Chinese databases such as CNKI,Wan Fang and Wei Pu,and foreign databases such as Pub Med,Medline,Cochrane and EMBASE,literatures related to the expression of PD-L1 and CCA were retrieved.The required literatures were screened out according to the inclusion and exclusion criteria,and the quality of the included literatures was evaluated by the newcastle-ottawa scale(NOS).Patients’ overall survival(OS)was analyzed,and the test effect size and test level were expressed as odds ratio(OR),risk ratio(HR)and 95% confidence interval(CI),respectively.Review Manager 5.3 and Stata11.0 software were used for Meta-analysis of the extracted data.Results: A total of 854 CCA patients were included in 7 cohort studies.The positive expression of PD-L1 in cholangiocarcinoma was associated with TNM stage(OR=2.23,95%CI: 1.27-3.91,P=0.005),but was not associated with gender(OR= 1.11,95%CI: 0.76-1.61,P=0.59),degree of differentiation(OR= 0.70,95%CI: 0.37-1.33,P=0.28),or lymph node metastasis(OR= 1.41,95%CI: 0.98-2.03,P=0.07).And infiltration depth(OR=0.75,95%CI:0.44-1.29,P=0.30),lymphatic invasion(OR=1.29,95%CI: 0.68-2.46,P=0.43),vascular invasion(OR=1.32,95%CI 0.36-4.85,P=0.68),and neural invasion(OR=1.08,95%CI: 0.53-2.18,P=0.84)were unrelated.Positive expression of PD-L1 was correlated with poor prognosis(HR= 1.68,95%CI:1.04-2.69,P=0.03),and subgroup analysis showed a significant correlation between PD-L1 expression and OS in extrahepatic cholangiocarcinoma(EHCC)(HR=2.08,95%CI: 1.28-3.38,P=0.003).Conclusion: The results of this meta-analysis indicate that the expression of PD-L1 may not be related to gender,differentiation degree,infiltration depth,lymph node metastasis,vascular,nerve or lymphatic infiltration.PD-L1 is associated with poor prognosis of cholangiocarcinoma,and the positive expression of PD-L1 is more likely to occur in advanced cholangiocarcinoma,which may be related to the negative regulation of PD-1 / PD-L1 pathway on the immune system,leading to tumor immune escape.It can be used as one of the monitoring indicators to evaluate prognosis in clinical practice.However,cholangiocarcinoma has a large heterogeneity,a complex tumor microenvironment.The expression mechanism of PD-L1 has not been fully clarified,and the existing research data are limited.Therefore,the clinical value of PD-L1 as a prognostic marker and in predicting the efficacy of immunocheckpoint inhibitors still needs to be confirmed by experimental studies on a larger scale. |
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