Aberrant expression of B7‑H4 may contribute to the development of hepatocellular carcinoma

Yuan,Lingling; Dong,Lijie; Yu,Guohua; Fan,Wanfeng; Zhang,Lin; Wang,Peiyuan; Hu,Xuemei; Zhao,Mingdong

doi:10.3892/mmr.2016.5887

Aberrant expression of B7‑H4 may contribute to the development of hepatocellular carcinoma

Authors:
- Lingling Yuan
- Lijie Dong
- Guohua Yu
- Wanfeng Fan
- Lin Zhang
- Peiyuan Wang
- Xuemei Hu
- Mingdong Zhao
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Affiliations: Department of Radiology, Binzhou Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong 256603, P.R. China, Department of Pathology, Yu Huang Ding Hospital, Yantai, Shandong 264000, P.R. China, Department of Immunology, Binzhou Medical University, Yantai, Shandong 264003, P.R. China
Published online on: October 25, 2016 https://doi.org/10.3892/mmr.2016.5887
Pages: 5015-5024
Copyright: © Yuan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

In order to determine the effect of B7‑H4 on the development of human hepatocellular carcinoma (HCC), the expression levels of B7‑H4 were evaluated using reverse transcription‑polymerase chain reaction and flow cytometry in HL‑7702 and Huh7 cells. B7‑H4 protein expression levels were analyzed using western blotting and immunohistochemistry in HCC tissues collected from patients and from a mouse tumor model. Soluble B7‑H4 (sB7‑H4), interferon‑γ (IFN‑γ), and interleukin‑4 (IL‑4) in blood serum were assessed using ELISA in patients with HCC and mice injected with tumor cells. B7‑H4 was expressed in HCC cell lines, mouse tumor tissues and HCC patient tissues. However, B7‑H4 was not detected in HL‑7702 cells or normal human liver tissues. The expression level of B7‑H4 was positively correlated with tumor‑node‑metastasis (TNM) stage, lymph node metastasis, and differentiation degree in patients with HCC. sB7‑H4 levels in blood serum samples collected from patients with HCC and tumorigenic mice were higher compared with healthy controls. Expression levels of IFN‑γ were reduced, and IL‑4 levels were increased in blood serum samples of patients with HCC and tumorigenic mice compared with healthy controls. sB7‑H4 expression levels were negatively correlated with IFN‑γ levels, and with the ratio of IFN‑γ to IL‑4. Additionally, sB7‑H4 was positively correlated with IL‑4 levels in mouse tumor tissues, serum samples obtained from tumorigenic mice and human HCC patients. Notably, the levels of sB7‑H4 and IL‑4 were positively correlated and IFN‑γ was negatively correlated with the TNM stage of patients with HCC. In addition, sB7‑H4 and IL‑4 expression levels increased and levels of IFN‑γ and the ratio of IFN‑γ/IL‑4 decreased as a function of time post tumor implantation in the mouse model. The present study determined that aberrant expression of B7‑H4 contributed to HCC development. B7‑H4 may be a potential target for therapy and diagnosis of HCC.

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