Does gene expression in laryngeal sub-sites differ between patients with laryngopharyngeal reflux and controls?

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 4 sub-sites (true vocal cord, false vocal cord, medial arytenoid, posterior commissure) of the larynx. qRT-PCR analyses were conducted on 20 reflux and inflammation related genes, including interleukin 6 and 8, cytokeratin 8 and 14, mucin genes MUC 1, 2, 3B, 4, 5B, 6 & 7, and carbonic anhydrase III. Statistical analysis (Mann Whitney U test) compared gene expression levels between LPR and control groups at each sub-site.

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 defense and inflammation, including CRNN, CD1d, TGFβ-1, MUC2, MUC5B, 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.

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