Does gene expression in laryngeal subsites 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 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, TGFb-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.

Pepsin promotes IL-8 signaling-induced epithelial–mesenchymal transition in laryngeal carcinoma

“…As the mean pH of the laryngopharynx is 6.8 [39, 40], the Hep-2 and Tu212 cells in the current study were exposed to pepsin at pH 7 and the proliferation and migration of the cells were assessed. Results from the current study provided strong evidence that pepsin promoted the proliferation and migration of Hep-2 and Tu212 cells in vitro.…”

RNA Sequencing Reveals Cancer‐Associated Changes in Laryngeal Cells Exposed to Non‐Acid Pepsin

“…57 Expression of mucosal defense and inflammatory response genes in LPR patients has demonstrated differences between glottis and supraglottis, and TVC relative to PC. 58,59 Accessibility and exposure to environmental factors may contribute to these disparities. Differences in the embryological origins of laryngeal subsites suggest that molecular characteristics intrinsic to the subsites may also play a role.…”

“…Within the glottis, carcinoma most frequently develops in the anterior vocal cords 56 while posterior commissure (PC) involvement is associated with aggressiveness and poorest prognosis 57 . Expression of mucosal defense and inflammatory response genes in LPR patients has demonstrated differences between glottis and supraglottis, and TVC relative to PC 58,59 . Accessibility and exposure to environmental factors may contribute to these disparities.…”

Laryngopharyngeal Reflux and Inflammatory Responses in Mucosal Barrier Dysfunction of the Upper Aerodigestive Tract

“…Muc3, a transmembrane mucin, is decreased in patients with LPR-associated inflammatory mucosa. 22,86 Specifically, Muc3A is thought to be a key factor in the maintenance of the epithelium under hypoxic conditions and in the regulation of cell migration and apoptosis during wound healing. 87 Muc1, another transmembrane mucin, has been shown to be highly expressed in patients with laryngeal dysplasia and laryngeal cancer.…”