The Expression And Significance Of PD-1 And TIM-3 In Hepatocellular Carcinoma

Objective:The present study detected the expression of PD-1(Programmed death-1,PD-1)and TIM-3(T-cell immunoglobulin domain and mucindomain containing molecule-3)in hepatocellular carcinoma(HCC)to analyse the relationship between them and each clinicopathological features,and the relationship between the two indicators.The study also analyzed the effect of the two indicators on prognosis,and evaluated the clinical significance of PD-1 and TIM-3 expression in HCC,thereby providing more theoretical basis for the clinical application of immune checkpoint inhibitor therapy for HCC patients.Methods:1.Collected 46 tissue wax blocks from patients with HCC who underwent surgical treatment in the 900th Hospital of the Joint Service and Security Force of the Chinese People’s Liberation Army from January 2013 to December 2015.Analysed case data and follow-up data of all patients retrospectively,all patients had complete case data and complete follow-up data..2.The expression of PD-1 and TIM-3 in cancer tissues and adjacent tissues were detected by immunohistochemical(IHC)staining,analyzed the correlation between the two proteins,and then analysed the correlation between the two proteins with clinicopathological features and prognosis.Results:1.The negative,weakly positive,moderately positive,and strongly positive expression rates of PD-1 in cancer tissues were respectively 26.09%(12/46),26.09%(12/46),41.30%(19/46),6.52%(3/46),and 60.87%(28/46),34.78%(16/46),4.35%(2/46),0.00%(0/46)in adjacent tissues,the comparison p=0.000<0.01.The negative,weakly positive,moderately positive,and strongly positive expression rates of TIM-3 in cancer tissues were respectively 8.70%(4/46),39.13%(18/46),39.13%(18/46),13.04%(6/46),and 15.22%(7/46),60.87%(28/46),21.74%(10/46),2.17%(1/46)in adjacent tissues,the comparison P=0.001<0.01.2.Spearman rank correlation analysis showed that the expression of PD-1 and TIM-3 in cancer tissues were correlated(rs=0.397,P=0.006).3.The expression level of PD-1 in cancer tissues was significantly correlated with tumor size(rs=0.480,P=0.001),portal vein tumor thrombus(rs=0.307,P=0.038),TNM stage(rs=0.5340,P=0.000)and AFP level(rs=0.400,P=0.006).The expression level of TIM-3 in cancer tissues was significantly correlated with portal vein tumor thrombus(rs=0.301,P=0.042),pathological differentiation(rs=0.356,P=0.015)and TNM stages(rs=0.416,P=0.004).4.The OS of 1 year,3 years and 5 years in 46 patients were 89.1%,56.5%and34.4%respectively,with average OS of 45.36±3.87 months and median OS of 39.0±3.4months.The DFS of 1 year,3 years and 5 years in 46 patients were 52.2%,21.7%and10.9%respectively,with average DFS of 23.41±3.52 months and median DFS of13.0±2.26 months.The single factor analysis showed that the expression levels of PD-1(χ~2=2.077,P=0.043),tumor size(χ~2=10.238,P=0.001),pathological differentiation degree(χ~2=13.939,P=0.001),TNM stage(χ~2=27.929,P=0.000)were the prognostic factors affecting the OS of HCC patients.The degree of pathological differentiation(χ~2=14.764,P=0.001)and TNM stage(χ~2=18.137,P=0.000)were the prognostic factors affecting the DFS of HCC patients.Multivariate analysis showed that pathological differentiation degree(HR=4.723,95%CI:1.952-11.428,P=0.001),tumor size(HR=3.234,95%CI:1.327-7.883,P=0.010),TNM stage(HR=3.254,95%CI:1.076-9.835,P=0.037),the expression level of TIM-3(HR=0.572,95%CI:0.329-0.995,P=0.048)were all independent prognostic factors of HCC patients’OS.Pathological differentiation degree(HR=2.945,95%CI:1.527-5.682,P=0.001)and TNM stage(HR=3.511,95%CI:1.259-9.793,P=0.016)were all independent prognostic factors of HCC patients’DFS.Conclusion:1.The expression level of PD-1 and TIM-3 in cancer tissues were higher than that in adjacent tissues.2.The expression level of PD-1 and TIM-3 in HCC tissues was positively correlated.3.The expression level of PD-1 in HCC tissues were correlated with tumor size,portal vein tumor thrombus and TNM stage.The expression levels of TIM-3 in HCC tissues were correlated with portal vein tumor thrombus,pathological differentiation degree and TNM stage,suggesting that the expression of PD-1 and TIM-3 may promote tumor progression.4.The high expression level of PD-1 and TIM-3 may predict poor prognosis in HCC patients.