Toll‑like receptor 4 and its associated proteins as prognostic factors for HCC treated by post‑radiotherapy surgery

Wu,Zhi‑Feng; Wang,Ying; Yang,Ping; Hou,Jia‑Zhou; Zhang,Jian‑Ying; Hu,Yong; Zeng,Zhao‑Chong

doi:10.3892/ol.2018.8583

Toll‑like receptor 4 and its associated proteins as prognostic factors for HCC treated by post‑radiotherapy surgery

Authors:
- Zhi‑Feng Wu
- Ying Wang
- Ping Yang
- Jia‑Zhou Hou
- Jian‑Ying Zhang
- Yong Hu
- Zhao‑Chong Zeng
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Affiliations: Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China, Department of Ultrasonography, Huashan Hospital, Fudan University, Shanghai 200032, P.R. China
Published online on: April 26, 2018 https://doi.org/10.3892/ol.2018.8583
Pages: 9599-9608
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Locally advanced hepatocellular carcinoma (HCC) treated by radiotherapy (RT) may be suited for further treatment with surgery. As a critical mediator of the post‑RT immune response, Toll‑like receptor 4 (TLR4) and its associated proteins may serve as prognostic factors for patients with HCC treated by post‑RT surgery. In the present study, a total of 20 patients with HCC treated by post‑RT surgery were enrolled. Resected tumor and peritumoral liver tissues were used to construct tissue microarrays that were assessed with immunohistochemical staining for the expression levels of TLR4, tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL) and vascular endothelial growth factor receptor 2 (VEGFR2). The overall (OS) and disease‑free (DFS) survival outcomes for each patient were assessed, and the severity of radiation‑induced liver diseases (RILDs) was detected. The patients with low TLR4 or TRAIL expression exhibited significantly better OS times than those with high TLR4 (P=0.003) or TRAIL (P=0.007) expression, whereas the median DFS times for patients with low VEGFR2 or TRAIL were significantly longer than those with high VEGFR2 (P=0.003) or TRAIL (P=0.008) expression. No significant differences in OS or DFS times were identified according to the expression of TLR4, VEGFR2 or TRAIL in peritumoral liver tissue, although more severe RILDs were identified in patients with the high expression of these factors in the peritumoral liver tissue post‑RT (P<0.05). Therefore, the expression levels of TLR4 and its associated proteins in HCC tumors may be suitable as prognostic factors for patients with HCC treated by post‑RT surgery. The inhibition of TLR4, VEGFR2 and TRAIL expression in HCC and non‑tumor liver tissue may lessen the severity of RILDs and improve survival outcomes in the future.

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