Expression And Significance Of IL-37 In Serum And Liver Tissues Of Patients With Hepatocellular Carcinoma

Objective:Interleukin-37(IL-37) is a new number of IL-1 family correlated with antiinflammatory cytokine. This study was to explore IL-37 expression in serum and liver tissues from hepatocellular carcinoma(HCC) patients, and discover the association between IL-37 expression and the clinicalpathological features such as age, gender, tumor size and so on. And then the function and mechanism of IL-37 in the pathogenesis of HCC was investigated. Methods:A total number of 36 HCC patients firstly covered and treated were collected from Tianjin Second People's Hospital between June 2014 and June 2015. All patients were confirmed as HCC with pathology, which derived from chronic HBV or HCV infection, including 24 cases in BCLC A and 12 cases in BCLC B. There were 28 patients with high-moderately differentiated HCC and 8 patients with poorly differentiated HCC. All HCC patients were prepared to accept liver resection or radiofrequency ablation therapy. Then 36 patients with liver cirrhosis and 36 healthy people were collected as controls.The serum levels of ALT, AST and TBIL were detected by automatic biochemical analyzer, and HBV serological markers and AFP were detected through electrochemical luminescence. The HBV DNA and HCV RNA were detected with real-time quantitative polymerase chain reaction(RT-q PCR). The HCV serological markers were detected using enzyme-linked immunosorbent assay(ELISA). Liver tissues from liver biopsy or surgery were sent to the pathology department and diagnosed by the pathologists.The expression of IL-37 was detected in serum and liver tissues using ELISA or immunohistochemistry(IHC). The expression of IL-37 in the serum was compared among the three groups(HCC patients, cirrhotic patients and healthy controls).In order to discover the relationship between IL-37 and clinicalpathological features such as age, gender, tumor size, BCLC stage, tumor histological differentiation, liver cirrhosis, HBV/HCV infection and serum AFP, HCC patients were stratified into two groups(low and high value groups) based on the expression value of IL-37. Results:1. There was no significant difference in serum IL-37 expression between patients with HCC, liver cirrhosis and healthy controls(P>0.05).2. In the liver tissues from HCC patients, IL-37 located in cytoplasm mainly expressed in the peri-tumoral tissues. However, there was no expression or low expression of IL-37 in most tumor tissues with the positive rate 47.2% compared with 100% in peri-tumoral tissues(P<0.05).3. IL-37 expression was only associated with tumor size(P<0.05). No correlations were found between the IL-37 expression and age, gender, BCLC stage, tumor histological differentiation, liver cirrhosis, HBV/ HCV infection, serum AFP(P>0.05).4. The tumor mass in low group was significantly larger than high group, which demonstrated that the expression value of IL-37 was negatively correlated with the tumor size. Conclusion:1. The serum IL-37 expression was influenced by many factors. The value of detecting IL-37 expression in tumor tissues was greater than in serum.2. The expression level of IL-37 was significantly lower in tumor tissues than the adjacent ones, and it was also negatively with tumor size. All the results indicated that IL-37 in tumor microenvironment played an important role in inhibiting tumorigenesis and could be applied into clinical practice as diagnostic biomarker and therapeutic target.