The Role And Mechanism Of IL-26 In The Development Of Hepatocellular Carcinoma

Objective: Inflammation has a great relationship with the occurrence and development of tumors.Although the role of the interleukin family in inflammation has been deeply studied,its specific role and mechanism in the development of tumors,especially liver cancer,still need to be further elaborated.As a new member of the IL-10 family,the role of IL-26 in tumors has almost not been reported.This study mainly explores the role and mechanism of IL-26 in hepatocellular carcinoma(HCC),which would provide a new potential target for basic research and clinical treatment.Methods: In the clinical sample analysis section,immunohistochemical(IHC)staining was performed on HCC specimens to analyze the expression of IL-26 in liver cancer;Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of IL-26 in serum of normal people,patients with viral hepatitis,cirrhosis and liver cancer;Western Blot was utlized to compare the expression of IL-26 in HCC specimens and adjacent tissues.The survival rate of patients in IL-26 high-expression group and lowexpression group was calculated by Kaplan-Meier method and compared by Log-rank method;Cox regression model was constructed to analyze the independent risk factors affecting patient survival rate.In the cell experiments,real-time quantitative polymerase chain reaction(RT-q PCR)and Western Blot were used to detect the expression levels of IL-26 and its receptors in HCC and normal liver cell lines.The effect of exogenous IL-26 on the proliferation of HCC cell lines was investigated by CCK8 assay.Transwell assay was used to explore the effect of exogenous IL-26 on the capacity of cell migration.The ELISA assay was used to compare the levels of IL-26 secreted by different normal liver cell lines and HCC cell lines.We adopted the hypoxia environment to simulate the living environment of HCC cells and added different cytokines to explore the conditions and possible mechanisms of IL-26 expression and secretion.P < 0.05 was considered statistically significant.Results: The level of IL-26 in the serum of normal population-hepatitis patients-patients with liver cirrhosis-liver cancer patients was gradually increased.Futhermore,it was highly expressed in HCC tissues.The level of IL-26 in the HCC tissues was negatively correlated with the overall survival(OS)and disease-free survival(DFS).Univariate and multivariate Cox regression analysis confirmed that high expression of IL-26 was an independent risk factor affecting OS and DFS in HCC patients.IL-26 was expressed and secreted by HCC cells.IL-26 and its receptors were expressed in HCC tissues and cell lines,but functional experiments showed that IL-26 did not regulate the proliferation and migration of HCC cells.Further mechanism experiments showed that IL-1? might promote the up-regulation of IL-26 expression in HCC cells by activating NF-k B pathway in hypoxic environment.Conclusions: IL-26 levels are negetivley related with the prognosis of HCC patients,which can be a potential prognostic molecule.However,IL-26 can not affect the proliferation and migration capacity of HCC cells.Its influence on the biological behavior of HCC needs further exploring,as well as its effect to HCC progression...