Expression Of Lymphocyte Activation Gene 3 In Hepatocellular Carcinoma And Its Clinical Significance

Background and PurposePrimary hepatic carcinoma is one of the most common malignant tumors in the world.Hepatocellular carcinoma(HCC)is the most common pathological type in primary liver cancer,accounting for 70%-90%.About 78% of HCC is caused by chronic infection of hepatitis B virus(HBV)and hepatitis C virus(HCV).At present,the most important treatments for liver cancer is hepatectomy,liver transplantation,transcatheter arterial chemoembolization(TACE)and local ablation therapy,but these traditional treatments encounter high postoperative recurrence rate,metastasis rate and high mortality rate.In addition to the above therapeutic measures,the current chemotherapy agent for liver cancer are only sorafenib and so on at home,but the median survival period is not optimistic.The tumorigenesis,development and metastasis of primary liver cancer are not only related to variety of gene mutations,but also complex mechanisms such as tumor cell immune escape in liver cancer tumor microenvironment.The research on immune checkpoint provides a new therapeutic option,immune targeted therapy for liver cancer,blocking the immune checkpoint,interrupting the immune escape of tumor cells,and repairing the function of tumor infiltrating lymphocytes to achieve the effect of anticancer therapy.Lymphocyte activation gene-3(LAG-3)is an immunosuppressive receptor involved in the tumorigenesis and development of various tumors including liver cancer.LAG-3 is a co-suppressor receptor that inhibits the activation of T cells and secretion of cytokines,ensuring immune homeostasis.At the same time,LAG-3 can prevent autoimmune diseases through maintaining immune homeostasis.LAG-3 plays an important function in tumor immune escape mechanism through regulation of T lymphocytes in the tumor microenvironment.In this study,immunohistochemical staining was used to detect the expression of LAG-3 in hepatocellular carcinoma(HCC)tissues,to explore the differences between clinical significance and LAG-3 expression,and provides evidence of immunotherapy for hepatocellular carcinoma in the future.Methods:A retrospective analysis on the clinical data was made for 150 patients with HCC underwent surgical treatment and confirmed by pathology in the Qingdao Municipal Hospital from February 27,2014 to January 12,2018.Of 150 specimens,120 are HCC specimens,and 30 specimens are adjacent normal liver tissue.150 cases of paraffin pathological samples were staining analyzed by means of immunohistochemical method and the staining results were evaluated by histochemical scoring criteria.Then use ?2 test to analyze the relationship between the expression level of LAG-3 in HCC and clinicopathological characteristics.Results:HCC tissues had high LAG-3 expression in 61 case(50.83%),low expression in 59 cases(49.17%).In adjacent normal tissues,high expression of LAG-3 in 7 cases(23.33%)and low expression of LAG-3 in 23 cases(76.67%).The difference between HCC tissues and adjacent normal tissues was statistically significant.The expression of LAG-3 in HCC was significantly higher than those in normal liver tissues(P<0.05).LAG-3 expression in HCC accouted for 26.19%(11/42)and 64.10%(50/78)in groups of specimen AFP ? 400 ng/ml and in groups of <400 ng/ml respectively;accounted for 36.84%(21/57)and 63.49%(40/63)in the groups of specimen tumor size ? 5 cm and < 5 cm;accounted for 71.79%(56/78)and 11.9%(5/42)in the groups of cirrhosis and in the groups of non-cirrhosis;accounted for 21.21%(7/33),62.67%(47/75)and 58.33%(7/12)in the groups of low,medium and high differentiation.Conclusion:1.HCC tissues had high LAG-3 expression,which was significantly higher than those of adjacent tissues.2.Several cases of LAG-3 positive expression were still detected in paracancerous tissues with a medical history of chronic HBV infection.Results show that during the chronic infection of HBV,the up-regulation of LAG-3 expression has been observed in HBV-associated lymphocytes,suggesting that immunotherapy may be effective for the treatment of HBV.3.The expression of LAG-3 in HCC tissues was not significantly different from gender,age,long-term drinking history,Child-Pugh classification,AFP level,ALT and AST level,cirrhosis,number of tumor,clinical stage of HCC.4.The expression of LAG-3 in HCC tissues was significantly different from different levels of preoperative AFP,different tumor sizes,and different tissue differentiation.Patients with large tumors,high AFP levels,and moderately differentiated tissues may be suitable for anti-LAG-3 antibody immunotherapy.