Lesion human leukocyte antigen-F expression is associated with a poor prognosis in patients with hepatocellular carcinoma

Abstract

Abstract. Human leukocyte antigen (HLA)-F, a non-classical HLA-class I molecule, has attracted attention as an important immunosuppressive molecule in recent years, although the clinical relevance of HLA-F expression in cancer patients remains unclear. In the present study, HLA-F expression in 90 primary hepatocellular carcinoma (HCC) lesions and 55 corresponding adjacent normal liver tissues was analyzed by immunohistochemistry, and the associations between HLA-F expression and clinicopathological parameters and patient survival times were analyzed. Positive HLA-F expression was observed in 47.8% (43/90) of the HCC lesions and in 10.9% (6/55) of the normal liver tissues. HLA-F expression in HCC lesions was significantly correlated with patient gender (P=0.02), and venous or lymphatic invasion (P=0.02). Patients who were HLA-F-positive had worse survival times than those who were HLA-F-negative (P=0.04). The mean overall survival times for HLA-F-negative and -positive patients were 44.2 months [95% confidence interval (CI), 37.7-50.7] and 33.0 months (95% CI, 25.1-40.8), respectively. Multivariate analysis revealed that HLA-F was an independent prognostic factor for HCC patients with a hazard ratio of 2.1 (95% CI, 1.0-4.4). In conclusion, the present study demonstrated that HLA-F expression was associated with poor survival in HCC patients, and is correlated with tumor cell invasion and metastasis.

Insulin resistance in obese adolescents affects the expression of genes associated with immune response

“…Islet hyperexpression of HLA class I molecules occurred in the insulin-containing islets of patients with recentonset type 1 diabetes and was also detectable in many patients with disease duration of up to 11 years, declining thereafter. Moreover, expression of HLA-F is correlated with tumor cell invasion and metastasis (Xu et al 2013;Ishigami et al 2015). HLA-F expression was found to be enhanced in gastric adenocarcinoma, breast cancer, esophageal squamous cell carcinoma, hepatocellular carcinoma, and neuroblastoma (Zhang et al 2013;Morandi et al 2013;Harada et al 2015;Martinez-Canales et al 2017;Wu et al 2018).…”

Immunobiology of HLA Class-Ib Molecules in Transplantation

“…Although HLA-F associates with β2m [48], no information is available on peptide presentation. It is thought to be biologically similar to other HLAIb molecules, such as in pregnancy [29,30] and cancer [32,49]; HLA-F also occurs in circulation as sHLA-F [32] like other sHLA-I molecules. However, the exact function of HLA-F remains to be elucidated.…”

HLA Loci and Respiratory Infectious Diseases

“…Despite expressing at cell surface at specific conditions and in particular cells, namely in activated lymphocytes, its most common expression is cytoplasmic [40,41] . HLA-F seems to be expressed in the first moments of the activation of an immune response and the evidences of its unusual properties, e.g., independent pathway to reach cell surface [42] and ability to bind bigger peptides [43] , point out for a different biological function than that of other class I molecules.…”