解剖取样部位与慢性鼻窦炎中TAS2R38基因表达无关：一项横断面RT-qPCR研究

文献信息

中文摘要

背景： 慢性鼻窦炎（CRS）是一种影响鼻窦黏膜的复杂炎症性疾病。苦味受体T2R38（由TAS2R38编码）表达于纤毛呼吸道上皮细胞，可检测细菌群体感应的酰基高丝氨酸内酯，从而刺激一氧化氮产生并加速黏液纤毛清除。然而，黏膜TAS2R38转录水平是否在不同鼻窦解剖区域间存在差异尚未得到验证，这引发了人们对转化气道研究中潜在取样偏倚的担忧。
目的： 确定在接受功能性内镜鼻窦手术（ESS）的CRS患者中，鼻窦黏膜TAS2R38基因表达是否在不同解剖亚部位间存在差异，并评估个体宿主生物学与活检部位之间的方差贡献。
方法： 在这项前瞻性横断面研究中，从67例手术CRS患者（符合EPOS 2020标准）的最多六个解剖部位（下鼻甲、上颌窦、筛窦、额窦、蝶窦和鼻息肉）采集了337份黏膜标本，同时采集了29份非炎症性鼻中隔对照标本。采用符合MIQE标准的RT-qPCR，以GAPDH为内参，定量相对TAS2R38 mRNA表达。采用以患者特异性随机截距为主要分析框架的线性混合效应模型评估聚类配对[公式：见正文]数据，并进行敏感性分析和倍数差异计算（[公式：见正文]）。
结果： 经过质量控制（因严格循环阈值和微量纤维组织产量而排除84份标本）后，分析了55例患者的253份有效标本（下鼻甲：n=52；上颌窦：n=50；筛窦：n=49；息肉：n=44；额窦：n=43；蝶窦：n=15）。各亚部位的平均[公式：见正文]值相当（范围：2.06至2.81；探索性ANOVA F=0.42，P=0.834）。在主要线性混合效应模型中，解剖取样部位与TAS2R38表达无关（[公式：见正文]）。个体间生物学方差（[公式：见正文]；ICC=0.333）显著超过个体内空间变异。在六种敏感性情景中验证了稳健性，包括排除蝶窦组织以及对年龄和性别的多变量调整（P=0.617）。病变黏膜相对于非部位匹配的鼻中隔对照，探索性显示上调2.48倍。
结论： 在手术CRS中，黏膜TAS2R38 mRNA表达与解剖取样部位无统计学显著关联，转录本变异性主要由患者间生物学差异驱动。这些发现提供了转化证据，支持下鼻甲活检作为研究鼻窦化学感觉先天防御的一种实用、可及替代方法的潜在效用。

英文摘要

BACKGROUND: Chronic rhinosinusitis (CRS) is a complex inflammatory condition affecting the sinonasal mucosa. The bitter taste receptor T2R38 (encoded by TAS2R38) is expressed on ciliated respiratory epithelial cells, detecting bacterial quorum-sensing acyl-homoserine lactones to stimulate nitric oxide production and accelerate mucociliary clearance. However, whether mucosal TAS2R38 transcript levels vary across distinct sinonasal anatomical niches remains unverified, raising concerns regarding potential sampling bias in translational airway research.
OBJECTIVE: To determine whether sinonasal mucosal TAS2R38 gene expression differs across anatomical sub-sites in patients with CRS undergoing functional endoscopic sinus surgery (ESS) and evaluate variance contributions between individual host biology and biopsy sites.
METHODS: In this prospective cross-sectional study, 337 mucosal specimens were harvested from up to six anatomical sites (inferior turbinate, maxillary, ethmoid, frontal, and sphenoid sinuses, and nasal polyps) in 67 surgical CRS patients (EPOS 2020 criteria), alongside 29 non-inflammatory septal control specimens. Relative TAS2R38 mRNA expression was quantified by MIQE-compliant RT-qPCR normalized to GAPDH. Clustered paired [Formula: see text]data were evaluated using linear mixed-effects modeling with patient-specific random intercepts as the principal analytical framework, alongside sensitivity analyses and fold-difference calculations ([Formula: see text]).
RESULTS: Following quality control (excluding 84 specimens due to strict cycle thresholds and minute fibrous tissue yield), 253 valid specimens across 55 patients were analyzed (inferior turbinate: n = 52; maxillary: n = 50; ethmoid: n = 49; polyps: n = 44; frontal: n = 43; sphenoid: n = 15). Mean [Formula: see text]values were comparable across subsites (range: 2.06 to 2.81; exploratory ANOVA F = 0.42, P = 0.834). In the principal linear mixed-effects model, anatomical sampling site was not associated with TAS2R38 expression ([Formula: see text]). Inter-individual biological variance ([Formula: see text]; ICC = 0.333) substantially exceeded intra-individual spatial variation. Robustness was verified across six sensitivity scenarios, including the exclusion of sphenoid tissues and multivariable adjustments for age and sex (P = 0.617). Diseased mucosa demonstrated an exploratory 2.48-fold upregulation relative to non-site-matched septal controls.
CONCLUSION: Mucosal TAS2R38 mRNA expression shows no statistically significant association with anatomical sampling site in surgical CRS, with transcript variability driven predominantly by between-patient biological differences. These findings provide translational evidence supporting the potential utility of inferior turbinate biopsy as a pragmatic, accessible surrogate for investigating sinonasal chemosensory innate defense.