肝细胞癌患者PBMCs TLR 2/4表达和小肠细菌过度生长对TACE术后生存期的影响

doi:10.3969/j.issn.1672-5069.2021.02.025

摘要/Abstract

摘要： 目的探讨肝细胞癌(HCC)患者外周血单个核细胞(PBMCs)表面Toll 样受体2(TLR2)和TLR4表达及小肠细菌过度生长(SIBO)对经肝动脉化疗栓塞(TACE)术后生存期的影响。方法 2013年1月～2016年6月我院诊治的47例HCC患者和同期在本院体检的100例健康人,所有患者接受TACE治疗。使用CytoFLEX流式细胞仪检测PBMCs表面TLR2和TLR4表达强度,采用乳果糖氢呼气试验(LHBT)法检测和评估SIBO。结果 HCC组SIBO阳性率为66.0%,显著高于健康人的6.0%(P＜0.05),PBMC表面TLR2⁺细胞表达强度为(94.7±12.3) GMF, 显著高于健康人【(26.4±4.2) GMF,P＜0.05】,TLR4⁺细胞表达强度为(43.1±8.7)GMF,显著高于健康人【(16.8±4.5) GMF,P＜0.05】;31例SIBO阳性HCC患者PBMCs表面TLR2⁺细胞为(109.3±16.8) GMF,显著高于16例SIBO阴性组【(71.5±5.6) GMF,P＜0.05】,TLR4⁺细胞为(46.7±7.1)GMF,显著高于SIBO阴性组【(31.5±4.3) GMF,P＜0.05】;除1例失访者外,23例长生存HCC患者在治疗后6个月PBMCs表面TLR2⁺细胞为(45.7±5.8)GMF,显著低于23例短生存组【(65.6±12.5)GMF,P＜0.05】,TLR4⁺细胞为(21.5±4.3)GMF,显著低于短生存组【(30.1±7.4) GMF,P＜0.05】,SIBO阳性率为4.4%,显著低于短生存组的62.5%(P＜0.05);23例TLR2高表达患者3 a累积生存率和3 a累积无事件生存率分别为17.4%和13.0%,显著低于23例TLR2低表达组的52.2%和43.5%(P＜0.05),23例TLR4高表达患者3 a累积生存率和3 a累积无事件生存率分别为13.0%和8.7%,也显著低于23例TLR4低表达组的56.5%和47.8%(P＜0.05),30例SIBO阳性患者3 a累积生存率和3 a累积无事件生存率分别为10.0%和3.3%,显著低于16例SIBO阴性患者的81.3%和75.0%(P＜0.05)。结论 HCC患者PBMCs表面TLR2和TLR4表达及SIBO可能影响TACE治疗的HCC患者的预后,其机制仍需要进一步研究。

关键词: 肝细胞癌, 肝动脉化疗栓塞术, 外周血单个核细胞, Toll 样受体, 小肠细菌过度生长, 生存

Abstract: Objective The aim of this study was to explore the impact of peripheral blood mononuclear cell (PBMC) surface Toll-like receptor (TLR) 2/4 expression and small intestinal bacterial overgrowth (SIBO) on survival in patients with hepatocellular carcinoma (HCC) after transcatheter arterial embolization (TACE) therapy.Methods A retrospective clinical analysis was performed in 47 patients with HCC, who received TACE in our hospital between January 2013 and June 2016. 100 healthy persons were recruited for the controls during the same period. The expression intensity (EI) of TLR2 and TLR4 on PBMC surface were detected by flow cytometry, and the SIBO was assessed based on lactulose hydrogen breath test (LHBT). patients with HCC was 66.0%, significantly.Results The SIBO positive rate in higher than 6.0%(P＜0.05) in healthy persons, and the EI of TLR2⁺ cells was (94.7±12.3)geometric mean fluorescence(GMF), significantly higher than 【(26.4±4.2) GMF, P＜0.05】, the EI of TLR4⁺ cells was (43.1±8.7)GMF, significantly higher than 【(16.8±4.5) GMF, P＜0.05】 in healthy persons; the EI of TLR2⁺ cells in 31 HCC patients with SIBO positive was (109.3±16.8) GMF, greater than【(71.5±5.6) GMF, P＜0.05】 in 16 HCC patients with SIBO negative, and the EI of TLR4⁺ cells was (46.7±7.1)GMF, greater than 【(31.5±4.3) GMF, P＜0.05】 in patients with SIBO negative; six month after TACE, the EI of TLR2⁺ cells in 23 but one patients who lost with long survival was (45.7±5.8)GMF, significantly weaker than 【(65.6±12.5)GMF, P＜0.05】, the EI of TLR4⁺ cells was (21.5±4.3)GMF, significantly weaker than 【(30.1±7.4) GMF, P＜0.05】 , and the SIBO positive rate was 4.4%, significantly lower than 62.5%(P＜0.05) in 23 patients with short survival; the 3-year cumulative survival rate and 3-year cumulative event-free survival rate in 23 patients with TLR2 intensified expression were 17.4% and 13.0%, significantly lower than 52.2% and 43.5%(P＜0.05) in 23 patients with weak TLR2 expression, and the 3-year cumulative survival rate and 3-year cumulative event-free survival rate in 23 patients with TLR4 strong expression were 13.0% and 8.7%, also significantly lower than 56.5% and 47.8%(P＜0.05) in 23 patients with weak TLR4 expression, and they were 10.0% and 3.3% in 30 patients with SIBO positive, significantly lower than 81.3% and 75.0%(P＜0.05) in 16 patients with SIBO negative. Conclusion The expression of TLR2 and TLR4 on PBMC surface and SIBO could impact the survival of patients with HCC after TACE, and the mechanism needs further investigation.

Key words: Hepatocellular carcinoma, Transcatheter arterial embolization, Peripheral blood mononuclear cells, Toll-like receptor, Small intestinal bacterial overgrowth, Survival

许超, 王森钰, 罗援烨, 陈王丽, 周芸, 盛以泉, 郭满盈. 肝细胞癌患者PBMCs TLR 2/4表达和小肠细菌过度生长对TACE术后生存期的影响[J]. 实用肝脏病杂志, 2021, 24(2): 248-251.

Xu Chao, Wang Senyu, Luo Yuanye, et al. Impact of PBMC surface TLR 2/4 expression and small intestinal bacterial overgrowth on survival in patients with hepatocellular carcinoma after TACE therapy[J]. Journal of Practical Hepatology, 2021, 24(2): 248-251.

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