Expression and clinical significance of immune checkpoint molecules HHLA2 and PD-L1 in hepatocellular carcinoma

ObjectiveTo explore the expression levels of immune checkpoint molecules human endogenous retrovirus-H long terminal repeat-associating protein 2(HHLA2) and programmed death ligand-1(PD-L1) in hepatocellular carcinoma(HCC) tissues, and analyze the correlation between HHLA2 and PD-L1 expression, and relationship between HHLA2 and PD-L1 expression, and clinicalpathological characteristics and prognosis.

MethodsThe expression levels of HHLA2 and PD-L1 in 90 human HCC tissues and corresponding adjacent tissues were detected using immunohistochemical staining.The correlation between the expression of HHLA2 and PD-L1 in HCC tissues was assessed.The relationship between the expression levels of HHLA2 and PD-L1, and clinical stage, serum α-fetoprotein(AFP) level, pathological grade, chronic hepatitis B virus infection, vascular invasion and over survival time(OS) were analyzed.

ResultsThe positive rates of HHLA2 in HCC tissues and adjacent tissues were 54.4% and 36.7%, respectively, and the difference of which was not statistically significant(P>0.05).The positive rates of PD-L1 in HCC tissues and adjacent tissues were 57.7% and 48.9%, respectively, and the difference of which was not statistically significant(P>0.05).The HHLA2 expression in HCC tissues was positively correlated with PD-L1 expression(r=0.280, P < 0.05).The expression of HHLA2 in HCC tissues was not related to the age, sex, pathological grade, serum AFP level and vascular invasion, but related to the clinical stage and chronic hepatitis B virus infection(P < 0.05).The expression of PD-L1 in patients with HCC was not associated with the age, sex, serum AFP level, vascular invasion and chronic hepatitis B virus infection, but associated with the clinical stage and pathological grade(P < 0.05).There was no statistical significance in OS between positive and negative HHLA2 and PD-L1 expression HCC patients(P>0.05).

ConclusionsThe expression levels of immune checkpoint molecules HHLA2 and PD-L1 in HCC tissues are on an upward trend, the expression of the two is positively correlated, and the expressions of HHLA2 and PD-L1 are not related to the prognosis of HCC patients.HHLA2, as a new immune checkpoint molecule, may be a potential therapeutic target for advanced liver cancer in the future, which still needs to be further studied.