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血清 Toll 样受体是局部晚期非小细胞肺癌放射性肺炎的潜在生物标志物。

Serum toll-like receptors are potential biomarkers of radiation pneumonia in locally advanced NSCLC.

作者信息

Lan Fengming, Yue Xiao, Ren Gang, Wang Yingjie, Xia Tingyi

机构信息

Department of Radiation Oncology, PLA Airforce General Hospital Beijing 100142, China ; Department of Radiation Oncology, Tianjin Hospital Tianjin 300190, China.

Tianjin Huanhu Hospital, Tianjin Neurosurgery Institute Tianjin 300060, China.

出版信息

Int J Clin Exp Pathol. 2014 Oct 15;7(11):8087-95. eCollection 2014.

PMID:25550856
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4270563/
Abstract

OBJECTIVE

Toll-like receptors (TLRs) are highly or lowly expressed in a wide variety of tumors and exhibit either pro-tumor or anti-tumor activities. In the present study, we investigate whether there are relationships between the expressions of TLRs and the occurrence of radiation pneumonia in advanced NSCLC patients treated with radiotherapy.

MATERIALS AND METHODS

76 patients diagnosed with NSCLC and 50 healthy controls were recruited from Oct 2012 to Jan 2014. The expressions of serum TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, and TLR9 were detected by ELISA techniques. Fisher exact test, χ(2) test, ROC working curve and Cox regression model were applied to analyze all data.

RESULTS

serum TLR1, TLR2, TLR4, and TLR9 exhibited a relative high expression level in NSCLC patients compared with healthy controls. Importantly, pre-neutrophil granulocyte ratio was associated with the expression of TLR1, TLR2, and TLR4. Moreover, the patients with high ratio of neutrophil granulocyte significantly increased the occurrence of fever in comparison to normal neutrophil ratio in NSCLC patients during the course of radiotherapy. We further evaluated the containing of TLRs when patients had temperatures and found serum TLR1, TLR2 and TLR4 were over-expressed. Finally, 26 of 76 patients were diagnosed with different stages of radiation induced pneumonia; as a result, the contents of TLR1 and TLR4 before radiotherapy were identified as independent significances with pneumonia occurrence.

CONCLUSIONS

The pretreatment levels of TLR1 and TLR4 have the predictive value to be clinically potential biomarkers of pneumonia risk in locally advanced NSCLC.

摘要

目的

toll样受体(TLRs)在多种肿瘤中高表达或低表达,具有促肿瘤或抗肿瘤活性。在本研究中,我们调查了TLRs表达与接受放疗的晚期非小细胞肺癌(NSCLC)患者放射性肺炎发生之间是否存在关联。

材料与方法

2012年10月至2014年1月招募了76例诊断为NSCLC的患者和50名健康对照。采用ELISA技术检测血清TLR1、TLR2、TLR3、TLR4、TLR5、TLR6、TLR7、TLR8和TLR9的表达。应用Fisher精确检验、χ²检验、ROC工作曲线和Cox回归模型分析所有数据。

结果

与健康对照相比,NSCLC患者血清TLR1、TLR2、TLR4和TLR9表现出相对较高的表达水平。重要的是,中性粒细胞前比值与TLR1、TLR2和TLR4的表达相关。此外,在放疗过程中,中性粒细胞比例高的NSCLC患者发热发生率明显高于正常中性粒细胞比例的患者。我们进一步评估了患者发热时TLRs的含量,发现血清TLR1、TLR2和TLR4过度表达。最后,76例患者中有26例被诊断为不同阶段的放射性肺炎;结果,放疗前TLR1和TLR4的含量被确定为与肺炎发生的独立显著因素。

结论

TLR1和TLR4的预处理水平对局部晚期NSCLC肺炎风险具有临床潜在生物标志物的预测价值。

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Knockdown of toll-like receptor 4 inhibits human NSCLC cancer cell growth and inflammatory cytokine secretion in vitro and in vivo.抑制Toll样受体4可在体外和体内抑制人非小细胞肺癌癌细胞的生长及炎性细胞因子的分泌。
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