Department of Clinical Pathology, South Egypt Cancer Institute, Assiut University, Assiut, Egypt.
Department of Clinical Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt.
Immunol Res. 2019 Jun;67(2-3):157-165. doi: 10.1007/s12026-019-09075-x.
Toll-like receptors (TLRs) have a role in chronic inflammation. Still, little is known about the expression of TLRs in hepatocellular carcinoma (HCC). Herein, we tried to assess the prognostic value of TLR2 and TLR4 expression on circulating monocytes in HCC patients and correlate their levels with some clinical, laboratory data, and treatment outcomes. Forty patients with hepatic focal lesions diagnosed radiologically as HCC by triphasic multislice CT pelviabdominal and chest, and in some patients MRI diffusion and 38 age and sex matching healthy controls were enrolled in the study. Subjects were evaluated for liver functions, alpha-fetoprotein (AFP), imaging, response to different treatments, and overall survival. TLR2 and TLR4 expression by monocytes was detected by flow cytometry. The expression of both TLR2 and TLR4 on monocytes was significantly increased in HCC patients than the controls, in patients with more progressive HCC than those with lower progression and in patients with poor response to treatment than patients with better treatment response. Moreover, their levels showed positive correlations with ALT, AST, and AFP and inverse correlations with the overall survival of HCC patients. The results of the current study suggest that increased expression ofTLR2 and TLR4 on peripheral monocytes might reflect the development and progression of HCC and can be used to indicate poor prognosis. In addition, high expression of TLR2 correlated significantly with poor response to treatment, while high expression of both TLR2 and TLR4 were associated with poor survival. Our findings will help to design more studies on the role of TLRs in HCC pathogenesis and prognosis which may provide new therapeutic targets for HCC.
Toll 样受体 (TLRs) 在慢性炎症中起作用。然而,关于 TLRs 在肝细胞癌 (HCC) 中的表达知之甚少。在此,我们试图评估 TLR2 和 TLR4 在 HCC 患者循环单核细胞中的表达对预后的影响,并将其水平与一些临床、实验室数据和治疗结果相关联。
本研究共纳入 40 名经影像学诊断为 HCC 的肝局灶性病变患者(通过三期多层 CT 盆腔和胸部,以及在一些患者中进行 MRI 扩散检查),并纳入 38 名年龄和性别匹配的健康对照者。对受试者进行肝功能、甲胎蛋白 (AFP)、影像学检查、对不同治疗方法的反应以及总生存期评估。采用流式细胞术检测单核细胞中 TLR2 和 TLR4 的表达。
与对照组相比,HCC 患者单核细胞中 TLR2 和 TLR4 的表达均显著增加,在 HCC 进展程度更高的患者中比进展程度较低的患者中增加,在对治疗反应较差的患者中比治疗反应较好的患者中增加。此外,它们的水平与 ALT、AST 和 AFP 呈正相关,与 HCC 患者的总生存期呈负相关。
本研究结果表明,外周血单核细胞中 TLR2 和 TLR4 的表达增加可能反映了 HCC 的发生和进展,并可用于预示不良预后。此外,TLR2 高表达与治疗反应不良显著相关,而 TLR2 和 TLR4 高表达均与生存不良相关。我们的发现将有助于设计更多关于 TLRs 在 HCC 发病机制和预后中的作用的研究,这可能为 HCC 提供新的治疗靶点。