Expression And Clinical Significance Of PD-1/L1,CD4~+CD25~+FoxP3~+ Treg In Hepatocellular Carcinoma

Objective To detect the expression of PD-1 ? PD-L1,CD4~+CD25~+FoxP3~+ Treg in HCC and analyze the relationship between the expression of PD-1?PD-L1,CD4~+CD25~+FoxP3~+ Treg and the prognoses of HCC patients.Methods In 2011~2013,we collect 106 cases of frozen specimens and 196 cases of paraffin embedded specimens with initial radical hepatic resection of HCC patients in the Affiliated Tumor Hospital of Guangxi Medical University.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect the expression of PD-1/L1 mRNA and Western Blotting and Immunohistochemistry was used to detect the expression of PD-1 ? PD-L1,CD4~+CD25~+FoxP3~+ Treg protein.Analyze the ralationships between the expression of PD-1?PD-L1,CD4~+CD25~+FoxP3~+ Treg and the prognoses of HCC patients.Results The expression of PD-1 ? PD-L1 mRNA and protein in carcinoma tissue was significantly higher than those in para-carcinoma tissue.High expression of PD-1 or PD-L1 was associated with several poor clinicopathologic factors,such as multiple nodules,Edmondson-Steiner stageIII/IV,and BCLC stage C.Patients with high expression of PD-1 or PD-L1 had significantly poor overall survival than those with low expression(P=0.048;P=0.015).However,patients with high or low expression of PD-1 or PD-L1 had similar disease-free survival(P=0.118;P=0.481).Patients with high or low expression of CD4~+CD25~+FoxP3~+ Treg had similar overall survival and disease-free survival(all P>0.05).Multivariate analysis found tumor diameter equal or more than 5 cm,multiple nodules,microvascular invasion,incomplete/absent tumor capsule,preoperative or postoperative alpha fetoprotein equal or more than 400 ng/ml,Edmondson-Steiner stage III/IV,BCLC stage C,tumor recurrence,and higher expression of PD-1 and PD-L1 were risk factors of deaths.In addition,tumor diameter equal or more than 5 cm,multiple nodules,microvascular invasion,incomplete/absent tumor capsule,preoperative or postoperative alpha fetoprotein equal or more than 400 ng/ml,and BCLC stage C were risk factors of tumor recurrence.Conclusions High expression of PD-1 ? PD-L1 and CD4~+CD25~+FoxP3~+ Treg are associated with several clinicopathologic characteristics.High expression of PD-1?PD-L1 and CD4~+CD25~+FoxP3~+ Treg are risk factors of tumor recurrence and death among patients with HCC after resection.