Prediction Of Lymph Node Metastases In Gastric Cancer By Serum APE1 Expression

Objective:Gastric cancer(GC)is one of most high mortality carcinoma in patients with poor prognosis.Screening early and efficacy biomarkers is critical for physicians to predict gastric cancer patients,metastasis and prognosis.Potential new serum maker candidates include vascular endothelial growth factor,cytokines and grovwth factors and other independent clinical prognostic predictors.Serum autoantibodies used as biomarkers are highly stable in blood,such as serum Her-2,seram Helicobacter pylori KatA and AhpC antibodies,for novel biomarkers in gastric cancer.Our study found that APE 1 protein overexpression is associated with poor overall survival of gastric cancer patients.In this study,based on our previous results,we aim to explore the relationship between serum APE 1 expression and gastric cancer lymph nodes involvement.We investigate the role of serum APE1 in further prediction of gastric cancer metastasis and prognosis.methods:Serum samples were pre-operational collected from 87 patients with gastric cancer from Affiliated Zhongshan Hospital of Dalian University from march 2015 to August 2016.The serum of APE1 was measured by ELISA development kit and other CA242,CA724,CA199 and CEA levels by electrochemiluminescence assay.And then we analyzed the APE 1 expression in 65 patients by IHC(immunohistochemically).Statistical analysis the results,and comparing with TCGA database.All the data analyzed by SPSS 19.0(IBM,Armonk,NY,USA)statistical software.Statistical significance by using nonparametric mann Whitney U test(differences)between different groups of decision.The receiver-operating characteristic(ROC)curve is made by the Medcalc software.The value of(P<0.05)in statistically significant.All inspection for bilateral,inspection level is 0.05,P<0.05 judged to be statistically significant.Results:The total of 87 patients with gastric cancer was classified into two groups(lymph node positive and negative groups).Using ELISA assay,we found out that the concentration of serum APE1 was higher in lymph node positive group than that of lymph node negative group(676.7±641.5 vs 386.7±360.5 ng/L)(P=0.023).The receiver operating characteristic(ROC)curve was performed to analyze,indicating that area under the ROC curve of serum APE 1 were better than those of each regular markers(CEA+CA199+CA242+CA724)or combination of these markers.The specificity of APE1(85.7%)was higher than CA242,CA724 and CEA(37.1%,57.1%and 82.9%),but lower than that of CA199(97.1%)in prediction of lymph node metastases.The cutoff value of APE1 was analyzed as 660.2.However,we found that serum APE1 has better diagnostic performance than that of each markers and even combination of other four markers(CEA+CA199+CA242+CA724).These data indicated that serum APE1 not only predicated lymph node metastases in gastric cancer but contribute to good performance in diagnosis.Additionally,we also search out the dataset of The Cancer Genome Atlas(TCGA)to have results of APE1 overexpression in tissues of primary site and lymph node metastases in 129 patients with gastric cancer.Among our patients,APE1 expression in tissue samples was stained in 65 samples of gastric cancer,comparing with control tissues.In this study,we find out APE 1 has higher expression in gastric cancer witih lymph node metastases than that of negative lymph node group(x 2=5.128,P=0.044),with a significant correlation with results of serum APE1 expression within the same cohort(r=0.262 P=0.035)Conclusion:we identified serum APE1 being a good marker for prediction of lymph node metastases in patients with gastric cancer.The detection of serum APE1 expression is helpful for the diagnosis and prognosis of lymph node metastasis in patients with gastric cancer.we found that serum APE1 has better diagnostic performance than that of each markers and even combination of other four markers(CEA+CA199+CA242+CA724).A statistical significant correlation was found between APE1 expression in tissue and peripheral blood and lymph node involvement in advanced gastric cancer.These findings provide clues that serum APE1 possess a potential to be a serum diagnostic marker for advanced gastric cancer.Further work shotuld focus on the prediction value on serum APE1 in prognosis of gastric cancer in a large cohort.