| Background and ObjectiveEsophageal cancer is a common malignant gastrointestinal tumor,with more than 480,000 new cases and 400,000 deaths worldwide each year.At present,the main treatment methods include surgery,chemotherapy,and radiotherapy.More than 90% of the pathological types of esophageal cancer in China are squamous cell carcinoma,and most of the patients are in the advanced stage at the time of initial diagnosis.They have lost the chance of surgery,with poor treatment effect and poor prognosis.In recent years,prognostic markers of esophageal squamous cell carcinoma have received increasing attention.Identifying key prognostic markers will help to analyze the prognosis of patients in different subgroups at the same stage.Programmed cell death-1(PD-1)/ programmed cell death ligand 1(PD-L1)pathway is one of the important mechanisms of immune escape of malignant tumors.The prognostic value of PD-L1 in esophageal squamous cell carcinoma remains controversial,but most researchs have confirmed that PD-L1-positive esophageal squamous cell carcinoma patients have a poor prognosis.PD-1 / PD-L1 is not only expressed on the cell membrane,but also in the blood.The soluble form is present,ie sPD-1 / sPD-L1.Studies have shown that tumor cells and bone marrow-derived cells such as macrophages and dendritic cells(DC)may be the source of sPD-L1,and the expression of serum spd-l1 is associated with systemic inflammatory responses,and can be affected by various inflammatory factors such as IL-10,IL-17 and TNF-α,etc.Serum sPD-L1 may be a marker of inflammation and immune regulation in the body.sPD-L1 can competitively bind to pd-1 receptor with pd-l1 on the cell membrane surface,and can also participate in blood circulation and bind to distant cell receptors,exerting a wide inhibitory effect and affecting the prognosis of malignant tumors.Recent studies have confirmed that serum sPD-L1 is associated with the prognosis of lung cancer,liver cancer and other tumors,but its prognostic significance in esophageal squamous cell carcinoma has rarely been studied.In this study,we examined the expression level of sPD-L1 and explored the prognostic value of sPD-L1 in patients with stage IV esophageal squamous cell carcinoma.At the same time,a nomogram prediction model was established based on prognostic indicators to guide clinical individualized and accurate treatment.MethodsOne hundred and fifty patients with stage IV esophageal squamous cell carcinoma diagnosed by biopsy pathology in the First Affiliated Hospital of Zhengzhou University from January 2015 to December 2016 were selected as the observation group,and 71 healthy people in the same period as the control group.The serum sPD-L1 levels of the control group and the observation group were measured by enzyme-linked immunosorbent assay(ELISA)before treatment.The optimal cut-off value of sPD-L1 was determined by plotting the ROC curve,and the patients were divided into the high expression level group and the low expression level group.Patients were divided into groups according to the level of inflammatory index NLR(neutrophil/lymphocyte ratio),weight loss(no or <5%,≥5%),and ECOG score(0,1),which were obtained through the electronic medical record system.Patients were divided into positive group and negative group respextively according to the expression levels of PD-L1,ki-67,P53,EGFR,VEGF and Her-2 in the tissues detected by immunohistochemical staining.The chi-square test was used to analyze the relationship between sPD-L1 and the clinicopathological parameters of the above patients with esophageal squamous cell carcinoma.Survival curves were drawn using kaplan-Meier to analyze the survival differences of patients with different expression groups.Univariate and multivariate analyses were performed using the COX risk regression model to screen independent risk factors for prognosis of patients with esophageal squamous cell carcinoma.The R-software was used to construct a nomogram model based on the independent predictors of stage IV esophageal squamous cell carcinoma,and the accuracy of the model was verified by calculating the consistency index and drawing the correction curve.Finally,patients were divided into high,medium and low risk groups according to the score of nomogram model,so as to verify the survival differences of patients in different risk groups and guide individualized treatment,and the survival difference of patients in different risk groups was analyzed to confirm the individualized prediction ability of the model.Results1.The serum sPD-L1 level in the esophageal cancer group was significantly higher than that in the healthy control group,and the difference was statistically significant(P<0.001).2.Correlation analysis indicated that the level of sPD-L1 was correlated with the level of NLR(P=0.004)and weight loss(P=0.036),but was not correlated with gender,age,tumor location,degree of differentiation,ECOG score,PD-L1,Ki-67,P53,EGFR,VEGF and Her-2(P>0.05).3.The optimal cut-off value of serum sPD-L1 was 264pg/ml by ROC curve.Survival analysis was performed according to the cut-off values.The results showed that in the progression-free survival(PFS)and overall survival(OS),the sPD-L1 high-level group was significantly shorter than the sPD-L1 low level(P=0.007,P<0.001);the NLR high level group was significantly shorter than the NLR low level group(P<0.001);the PD-L1 positive group was significantly shorter than the PD-L1 negative group(P=0.016,P=0.021).The high expression group of Ki-67 was significantly shorter than the low expression group(P=0.006,P=0.002);The P53 positive group was significantly shorter than the negative group(P=0.001,P=0.008);Compared with patients without weight loss or with weight loss <5%,patients with weight loss ≥5% have shorter PFS and OS(P=0.004,P=0.009);There was no difference in PFS and OS among the EGFR,VEGF,Her-2 different expression groups and different ECOG score groups(0,1)(P>0.05).4.Univariate analysis of COX risk ratio model suggested that: sPD-L1,NLR,PD-L1,Ki-67,P53 and weight loss were all factors affecting the prognosis of patients with stage IV esophageal squamous cell carcinoma(P<0.05);Multivariate analysis suggested that sPD-L1,NLR,Ki-67,and weight loss were independent prognostic factors for patients with stage IV esophageal squamous cell carcinoma(P<0.05).5.Based on the independent prognostic factors of patients with stage IV esophageal squamous cell carcinoma,a nomogram prediction model was constructed by using the R software.The internal verification of the model showed that the consistency index(c-index)of the nomogram prediction model in this study was 0.74(95% CI: 0.68-0.79),with good consistency.6.The patients were divided into high,medium and low risk groups by the nomogram model.The survival analysis results indicated that there were significant differences among the three groups(P=0.008),which further verified the accuracy of this prediction model.Conclusion1.Serum sPD-L1 can be an independent prognostic indicator for patients with stage IV esophageal squamous cell carcinoma.2.The sPD-L1-based nomogram model can accurately predict the prognosis of patients with stage IV esophageal squamous cell carcinoma,which has high clinical application value. |
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