Expression Of SOCS1 And JAK1 MRNA In Peripheral Blood Of Patients With Hepatitis B Virus-associated Hepatocellular Carcinoma And Their Relationship With Treg/Th17 Imbalance

Objective(s):To investigate the balance of regulatory T cells(Treg)and helper T cells 17(Th17)in peripheral blood of hepatitis B virus-associated hepatocellular carcinoma(HBV-HCC)patients,as well as the mRNA expression of suppressor of cytokine signaling 1(SOCS1)and janus kinase 1(JAK1),and to explore the effect of the latter on Treg/Th17 imbalance.Methods:From February to August 2022,28 patients with HBV-HCC who were admitted to the outpatient clinic and hospitalization of the Department of Geriatric Gastroenterology of the First Affiliated Hospital of Kunming Medical University were selected as the study subjects,and 18 healthy physical examinees in the same period were selected as normal control groups.Flow cytometry(FCM)was used to detect the frequency of Treg and Th17 cells in peripheral blood CD4~+T cells;Enzyme linked immunosorbent assay(ELISA)detected the expression levels of cytokines interleukin-10(IL-10),IL-2,IL-17A and IL-21;Real-time fluorescence quantitative reverse transcription polymerase chain reaction(q RT-PCR)was used to determine peripheral blood SOCS1,JAK1,forkhead/winged helix transcription 3 Factor 3(Fox P3),retinoid related orphan nuclear receptorγt(RORγt)mRNA expression levels.Results:1.The percentage of Treg cells,Th17 cells among CD4~+T cells,Treg/Th17 ratio and the expression levels of cytokines IL-10,IL-2,IL-17A and IL-21in peripheral blood of HBV-HCC patients were higher than those in normal control group(all P<0.05).In the HBV-HCC group,the percentage of Treg cells among CD4~+T cells、Treg/Th17 ratio and cytokine IL-10 expression levels in peripheral blood of patients in the CNLC stage IIIa and above group were higher those in the below the CNLC stage IIIa group(all P<0.05);the percentage of peripheral blood Treg cells in CD4~+T cells and the expression level of cytokine IL-10 were higher in the high viral load group(HBV DNA quantification≥1×10~5IU/m L)than in the low viral load group(HBV DNA quantification<1×10~5IU/m L)(all P values<0.05).The percentage of Treg cells and Th17 cells in CD4~+T cells in the peripheral blood of patients with HBV-HCC was positively correlated with the level of lg HBV-DNA(all P<0.05).2.In the HBV-HCC group,the expression levels of SOCS1 mRNA in peripheral blood were lower than those in the normal control group,while the expression levels of JAK1,Fox P3 and RORγt mRNA were higher than those in the normal control group(all P<0.05).In the HBV-HCC group,the expression levels of JAK1,Fox P3 and RORγt mRNA in the peripheral blood of patients in the CNLC stage IIIa and above group were higher than those in the below the CNLC stage IIIa group(all P<0.05).The expression levels of SOCS1 mRNA in peripheral blood of patients in the high viral load group were lower than those in the low viral load group,while Fox P3 mRNA was higher than that in the low viral load group(all P<0.05).The expression levels of Fox P3 and RORγt mRNA in peripheral blood of patients with HBV-HCC were positively correlated with lg HBV-DNA levels(all P<0.05).3.The expression levels of SOCS1 mRNA in peripheral blood of HBV-HCC patients were negatively correlated with Treg/Th17 ratio and positively correlated with IL-21 expression levels(all P<0.05);JAK1 mRNA expression levels were positively correlated with Treg/Th17 ratio,Fox P3 mRNA,RORγt mRNA and IL-10 expression levels,and negatively correlated with IL-17A(all P<0.05).Conclusion(s):1.There is a Treg/Th17 imbalance in the peripheral blood of HBV-HCC patients dominated by elevated Treg cells,and the proportion of Treg cells in CD4~+T cells is positively correlated with the level of HBV replication.2.The low expression of SOCS1 mRNA and the high expression of JAK1 mRNA in peripheral blood of patients with HBV-HCC may be related to the imbalance of Treg/Th17.