Purpose
To investigate whether progression, immune status and prognosis of hepatocellular carcinoma (HCC) are related to the subtype and expression of apolipoprotein E (apoE).
Methods.
Immunofluorescence staining of CD11b+/LOX1+and CD14+/HLA-DR- combinations was performed on the tissue microarrays of tumor samples from 360 HCC patients to assess the abundance of infiltrating polymorphonuclear granulocyte-like myeloid-derived suppressor cells (PMN-MDSCs) and monocyte-like MDSCs (M-MDSCs). Immunohistochemistry was used to evaluate the expression of apoE2, apoE3, apoE4, arginase (ARG) and inducible nitric oxide synthase (iNOS). Univariate, multivariate COX regression, and the Kaplan-Meier methods were used to evaluate the survival. Peripheral blood samples were collected and divided into three groups according to blood apoE level in the second cohort. Flow cytometry method detected immune cells abundance.
Results
COX regression analysis showed H-score of apoE2 in tumour tissue below 16.01 (HR=6.140, p=0.00005) and H-score of apoE4 above 4.05 (HR=7.001, p=0.009) were significantly associated with shorter overall survival (OS). The density of infiltrated PMN-MDSCs (>2.87 cells/mm2 (HR=3.762, p=0.000009)) and proportion of M-MDSCs of total cells (<89.32% (HR=0.454, p=0.006)) in tumour tissue were independent risk factors for shorter recurrence-free survival (RFS). The low apoE group had a higher abundance of MDSCs in the peripheral blood compared to the normal and high blood apoE levels. The number of CD14+HLA-DR-/low M-MDSCs (p=0.0399) were higher than in the apoE high level group. Higher level of CTLA-4+ T lymphocytes were detected in the low apoE group than in the normal group.
Conclusion
The abundance of MDSCs, CTLA-4+ T lymphocytes in the peripheral blood from HCC patient was negatively correlated with the level of apoE. ApoE4 suggests poor prognosis, but apoE2 may be a potential protective factor for HCC patient’s OS.