Expression Of Tim-4 And Its Relationship With Tissue Differentiation And Prognosis In Hepatocellular Carcinoma

Background and objectiveEpidemiology shows that primary liver cancer is the sixth most common cancer in the world and the third leading cause of cancer death.In our country,the number of patients with liver cancer is basically among the top five,and the mortality rate is still very higher.Liver cancer poses a huge threat to the health and lives of our people.Although more and more attention has been paid to liver cancer year by year,the onset of liver cancer is latent and the treatment methods are limited.There is still an urgent need to solve the problem of poor prognosis of liver cancer.Targeted therapy and immunotherapy are currently two hot spots in the treatment of advanced liver cancer.Searching for effective targets is an important development direction of advanced liver cancer therapy.Primary liver cancer is a kind of tumor with extremely malignant biological behavior,and hepatocellular carcinoma(HCC)is the most common type of primary liver cancer.T-cell immunoglobulin and mucin protein(Tim)family is an emerging family of immunoregulatory factors.Tim-4,as a member of Tim family,is mainly expressed on antigen-presenting cells.Tim-4 may regulate T-cell immune response by binding to correlative receptors and is closely related to allergic diseases,autoimmune diseases,transplant tolerance and cancer.Researchers have found that overexpression of Tim-4 in some tumor tissues plays an important role in tumor occurrence,development and treatment.Overexpression of Tim-4 in tumor-associated myeloid cells can promote tumor progression,metastasis and immune tolerance through a variety of mechanisms and interactions with cytokines,as well as enhance the tolerance of anti-tumor drugs and resistance to tumor radiotherapy.Tim-4 is also associated with poor prognosis of tumor patients.However,some studies have shown that the expression of Tim-4 on Bel cells can inhibit the development of melanoma and reduce the rate of pulmonary metastasis.Whether stimulative or suppressive effects of Tim-4 in tumors may be related to the location of the tumor and the pathogenic causes.At present,it is still unclear about the expression of Tim-4 in hepatocellular carcinoma and its relationship with the prognosis of hepatocellular carcinoma patients.Therefore,this article will explore about these.MethodsIn this study,immunohistochemical staining method was used to detect the expression level of Tim-4 in tumor tissue and adjacent non-tumor tissue of the microarrays about 90 patients with hepatocellular carcinoma,and we compared the difference between them.Then,we analyzed these 90 patients of the relationship between the clinical features data and the expression of Tim-4 in tumor tissue of hepatocellular carcinoma.Finally,the survival analysis was carried out.The data were presented as mean,median and 95%confidence intervals.SPSS 25.0 statistical software was utilized to analyze the statistical data,and we used Chi-square test and Fisher’s exact test,Log-Rank test and Cox proportional hazards regression model to process the data.The significance test standard a is 0.05 or 0.01.Results1.Compared with the corresponding adjacent non-tumor tissue,Tim-4 was significantly down-regulated in the tumor tissue of hepatocellular carcinoma(P<0.01);2.The expression of Tim-4 was related to the differentiation and PD-L1 expression of tumor tissue in hepatocellular carcinoma,and the degree of tumor tissue differentiation was better in patients with Tim-4 positive expression(P<0.05).But Tim-4 was irrelevant to the gender,age,liver cirrhosis,TNM staging,tumor size and recurrence(P>0.05);3.Univariate survival analysis showed that the 3-year,4-year,5-year and disease-free survival time of hepatocellular carcinoma patients with the positive expression of Tim-4 in tumor tissue was longer than that of patients with negative expression(P<0.05),the positive expression of Tim-4 in tumor tissue may be an indicator of good prognosis in patients with hepatocellular carcinoma.ConclusionIn hepatocellular carcinoma,the expression of Tim-4 in tumor tissue is significantly lower than that of adjacent tissues.The expression level of Tim-4 is positively correlated with the tumor tissue differentiation and may be an indicator of good prognosis in patients with hepatocellular carcinoma.