Toll-like receptor expression in human non-small cell lung carcinoma: potential prognostic indicators of disease.

Toll-like receptor expression in human non-small cell lung carcinoma: potential prognostic indicators of disease.
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DOI:
10.18632/oncotarget.19463
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发表时间:
2017-11-03
期刊:
影响因子:
--
通讯作者:
Wiese D
Wiese D
中科院分区:
其他
文献类型:
--
作者:
Bauer AK;Upham BL;Rondini EA;Tennis MA;Velmuragan K;Wiese D

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肺癌仍然是全世界癌症死亡率最高的原因。Toll样受体(TLR)是具有促肿瘤发生和抗肿瘤发生特性的先天性免疫受体。基于流行病学研究和啮齿类动物的发现,我们假设TLR表达升高是非小细胞肺癌患者疾病的积极预后指标。当在非小细胞肺癌(NSCLC)患者和腺癌(ADC)亚型中单独或作为一组进行分析时,TLR 1 -3和5-8的较高mRNA表达与总生存期(OS)增加显著相关。通过RNA测序还观察到ADC患者中许多TLR组合的显著共表达。免疫组化显示TLR 4和TLR 8在肿瘤组织中具有显著相关性,类似于RNA。我们使用kmplot.com对TLR 1 -10的mRNA表达进行荟萃分析,以确定NSCLC和ADC亚型与OS的任何显著相关性。cBioportal还同时用于通过RNA测序评估ADC患者中TLR 1 -10的共表达,并鉴定任何分子改变。最后,对ADC患者进行TLR亚组的免疫染色。先天性免疫受体TLR 1 -10的表达与NSCLC生存结局改善相关。因此,进一步评估其预测能力和治疗效用是必要的。
Lung cancer remains the highest cause of cancer mortality worldwide. Toll-like receptors (TLR) are innate immune receptors that have both pro- and anti-tumorigenic properties. Based on findings from epidemiological studies and in rodents, we hypothesized that elevated TLR expression would be a positive prognostic indicator of disease in non-small cell lung carcinoma patients. Higher mRNA expression of TLR1-3 and 5-8 were significantly associated with increased overall survival (OS) when analyzed individually or as a group in both non-small cell lung carcinoma (NSCLC) patients and in the adenocarcinoma (ADC) subtype. Significant co-expression of many TLR combinations in ADC patients were also observed via RNA sequencing. Immunostaining demonstrated TLR4 and 8 significantly correlated in tumor tissue, similar to RNA. We used kmplot.com to perform a meta-analysis on mRNA expression of TLR1-10 to determine any significant associations with OS in NSCLC and the ADC subtype. cBioportal was also used simultaneously to assess co-expression in TLR1-10 in ADC patients via RNA sequencing and to identify any molecular alterations. Lastly, immunostaining for a subset of TLRs was conducted on ADC patients. Expression of innate immune receptors TLR1-10 is associated with improved survival outcomes in NSCLC. Thus, further evaluation of their predictive capacity and therapeutic utility is warranted.
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