Correlation Study Of Interleukin-33 And Vascular Endothelial Growth Factor C In Liver Metastasis Of Gastric Cancer

Background and objectiveIn recent years,with the improvement and popularization of endoscopic techniques,especially in middle-aged people with high risk factors of gastric cancer such as chronic atrophic gastritis,gastric ulcer patients,early diagnosis and treatment can prevent the occurrence of gastric cancer,but the complications caused by rapid tumor growth and distant metastasis make the mortality still high.The early diagnosis of gastric cancer and monitor of metastasis is an urgent problem to be solved.Therefore,it is the focus of clinical and basic research to actively find an effective marker for the diagnosis and judgment of gastric cancer progression.Inflammation not only induces tumorigenesis,but also promotes tumor development and metastasis.A large number of inflammatory cells and inflammatory factors existing in tumor microenvironment will induce a variety of cytokines and chemokines expression,promote cell proliferation and induce angiogenesis,such that the tumor can be rapid growth and at the same time provide conditions for the distant metastasis of the tumor.The aim of this study was to investigate the expression of interleukin-33 and vascular endothelial growth factor C in serum and tissue samples of gastric cancer patients,and to analyze the correlation between the expression of IL-33 and VEGF-C in gastric cancer with clinicopathological factors,lymph node metastasis and liver metastasis,to investigate the value of monitoring IL-33 and VEGF-C in assessing the progression and prognosis of gastric cancer patients,and to provide the theoretical basis for clinical comprehensive treatment of gastric cancer with liver metastases.Materials and MethodsPatients(N=98)were enrolled into this study with histopathology confirmed gastric cancer.All patients enrolled were inpatients from January 2012 to December 2014 diagnosed in affiliated Jiangsu Cancer Hospital of Nanjing Medical University who underwent surgical treatment for the first time and were tested for serum IL-33 and VEGF-C levels before treatment.At the same time,36 healthy subjects who accepted physical examination in our hospital for the same period were selected as the control group.We also collected demographic characteristics,clinicopathologic characteristics and laboratory indexes by looking up medical records.The expression of IL-33 and VEGF-C in serum samples were detected by enzyme-linked immunosorbent assay(ELISA).The expression of IL-33 and VEGF-C in tissue samples were detected by immunohistochemical staining.To investigate the correlation between clinicopathological factors and IL-33 as well as VEGF-C expression in order to determine whether IL-33 and VEGF-C can be used as a serum tumor marker for monitoring and prognosis of gastric cancer.Results(1)The expression rate of IL-33 and VEGF-C in gastric cancer is 67.35%and 74.49%,significantly higher than that in normal gastric tissue(47.22%and 61.11%),the difference is statistically significant(P<0.001).There is no statistical significance between the difference of IL-33 and VEGF-C expression in the patients' genders,ages,tumor locations and tumor sizes(P>0.05),while the degree of tumor differentiation,tissue infiltration,lymph node metastasis,distant metastasis and clinical stage differences shows a significant statistical difference(P<0.05).The IL-33 and VEGF-C expression rate in the lymph node metastasis group is higher than that in the group which lymph node metastasis does not occur(P=0.044,0.028).The IL-33 and VEGF-C expression rate in liver metastasis group is higher than that in the group without liver metastasis(P=0.004,0.001).(2)The levels of serum IL-33 and VEGF-C in patients with gastric cancer were 50.24 � 13.08pg/ml and 210.73 � 58.35 pg/ml respectively,which was higher than that in healthy control group.The levels of serum IL-33 and VEGF-C in lymph node metastasis group were higher than those in non-lymph node.The levels of IL-33 and VEGF-C in the liver metastasis group were significantly higher than those in the non-liver metastasis group(P<0.05).The serum levels of IL-33 and VEGF-C were positively correlated.(3)The median survival time of IL-33 and VEGF-C positive group was 23.7 months and 24.5 months respectively,compared with the negative group the survival time was shortened(P = 0.029,0.021).Multivariate analysis showed that tissue invasion T3-T4,lymph node metastasis,liver metastasis,positive expression of IL-33 and VEGF-C were the prognostic factors of gastric cancer(P<0.05).Conclusions(1)The expression of IL-33 and VEGF-C in the tissues and serum of patients with gastric cancer were higher than those in the healthy control group.The expression level of IL-33 and VEGF-C was positively correlated with lymph node metastasis,liver metastasis and prognosis.(2)The expression of IL-33 and VEGF-C in serum of patients with gastric cancer was increased at the same time,and the expression level of IL-33 was positively correlated with the expression of VEGF-C,which participate in the regulation of invasion and metastasis of gastric cancer together.(3)When the expression of IL-33 and VEGF-C is positive,the incidence of liver metastasis is high and the prognosis is poor,which can provide certain reference value for the clinical treatment of patients with liver metastases.