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喉咽反流患者与对照组之间喉部分部位的基因表达是否存在差异?

Does gene expression in laryngeal subsites differ between patients with laryngopharyngeal reflux and controls?

作者信息

Wood J M, Hussey D J, Woods C M, Astill D, I Watson D, Lee B, Carney A S

机构信息

Flinders ENT, Adelaide, SA, Australia.

Flinders University Department of Surgery, Flinders Centre for Cancer Prevention and Control, Adelaide, SA, Australia.

出版信息

Clin Otolaryngol. 2018 Feb;43(1):158-163. doi: 10.1111/coa.12918. Epub 2017 Jul 4.

Abstract

OBJECTIVE

To identify laryngeal mRNA gene changes in patients with laryngopharyngeal reflux (LPR).

METHOD

Laryngeal biopsies from non-smoking LPR patients (n=10; Reflux Symptom Index (RSI) >12 and a Reflux Finding Score (RFS) >6) and controls (n=9; RSI <12 and RFS <6) were collected from four subsites (true vocal cord, false vocal cord, medial arytenoid and posterior commissure) of the larynx. qRT-PCR analyses were conducted on 20 reflux- and inflammation-related genes, including interleukins 6 and 8, cytokeratins 8 and 14, mucin genes MUC1, MUC2, MUC3B, MUC4, MUC5B, MUC6 and MUC7 and carbonic anhydrase III. Statistical analysis (Mann-Whitney U test) compared gene expression levels between LPR and control groups at each subsite.

RESULTS

Site-specific differences in squamous metaplasia and gene expression were noted in LPR patients, with the majority present in the medial arytenoid region. Significant.differences were noted in genes related to mucosal defence and inflammation, including CRNN, CD1d, TGFβ-1, MUC2, MUC5B and CDH1.

CONCLUSION

Whilst the posterior commissure is commonly identified as the area demonstrating the most significant macroscopic change in LPR, the histological changes and genes assessed here showed more pronounced LPR associated differences in the medial arytenoid. We identified differences in expression of mucin genes, cytokeratin-14 and molecular markers of inflammation. Whilst some of these changes may be metaplasia-related, further evaluation of the mRNA expression of these genes may provide a useful biomarker panel for diagnosis and therapeutic monitoring of LPR.

摘要

目的

确定喉咽反流(LPR)患者喉部的mRNA基因变化。

方法

从非吸烟LPR患者(n = 10;反流症状指数(RSI)> 12且反流发现评分(RFS)> 6)和对照组(n = 9;RSI < 12且RFS < 6)的喉部四个亚部位(真声带、假声带、杓状软骨内侧和后联合)采集活检样本。对20个与反流和炎症相关的基因进行qRT-PCR分析,包括白细胞介素6和8、细胞角蛋白8和14、粘蛋白基因MUC1、MUC2、MUC3B、MUC4、MUC5B、MUC6和MUC7以及碳酸酐酶III。采用统计分析(曼-惠特尼U检验)比较LPR组和对照组在每个亚部位的基因表达水平。

结果

在LPR患者中观察到鳞状化生和基因表达的部位特异性差异,大多数存在于杓状软骨内侧区域。在与黏膜防御和炎症相关的基因中发现了显著差异,包括CRNN、CD1d、TGFβ - 1、MUC2、MUC5B和CDH1。

结论

虽然后联合通常被认为是LPR中显示最显著宏观变化的区域,但此处评估的组织学变化和基因显示,杓状软骨内侧的LPR相关差异更为明显。我们发现了粘蛋白基因、细胞角蛋白-14和炎症分子标志物表达的差异。虽然其中一些变化可能与化生有关,但对这些基因的mRNA表达进行进一步评估可能为LPR的诊断和治疗监测提供一个有用的生物标志物组。

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