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人非小细胞肺癌中Toll样受体的表达:疾病的潜在预后指标

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

作者信息

Bauer Alison K, Upham Brad L, Rondini Elizabeth A, Tennis Meredith A, Velmuragan Kalpana, Wiese David

机构信息

Department of Environmental and Occupational Health, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

Department of Pediatrics and Human Development, Michigan State University, East Lansing, MI 48824, USA.

出版信息

Oncotarget. 2017 Jul 22;8(54):91860-91875. doi: 10.18632/oncotarget.19463. eCollection 2017 Nov 3.

Abstract

INTRODUCTION

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.

RESULTS

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.

METHODS

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.

CONCLUSIONS

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.

摘要

引言

肺癌仍是全球癌症死亡的首要原因。Toll样受体(TLR)是先天性免疫受体,具有促肿瘤和抗肿瘤特性。基于流行病学研究结果及在啮齿动物中的研究,我们假设TLR表达升高是非小细胞肺癌患者疾病的阳性预后指标。

结果

在非小细胞肺癌(NSCLC)患者和腺癌(ADC)亚型中,单独分析或作为一组分析时,TLR1-3和5-8的较高mRNA表达均与总生存期(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。免疫染色显示,肿瘤组织中TLR4和8显著相关,与RNA情况相似。

方法

我们使用kmplot.com对TLR1-10的mRNA表达进行荟萃分析,以确定与NSCLC和ADC亚型的OS是否存在任何显著关联。同时还使用cBioportal通过RNA测序评估ADC患者中TLR1-10的共表达,并识别任何分子改变。最后,对ADC患者进行了部分TLR的免疫染色。

结论

先天性免疫受体TLR1-10的表达与NSCLC患者的生存结果改善相关。因此,有必要进一步评估它们的预测能力和治疗效用。

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