Long-term defects of nasal epithelium barrier functions in patients with nasopharyngeal carcinoma post chemo-radiotherapy.

• Chemo-radiotherapy induces long-term defects in nasal epithelial barrier functions. • The defects in nasal epithelium cause sinonasal mucosal infection and inflammation. • Damage of nasal epithelial stem/progenitor cells were found in barrier dysfunction. • Promote nasal epithelial stem/progenitor cells may contribute to recover the barrier. Chronic and recurrent upper respiratory tract infection and inflammation is common in patients with nasopharyngeal carcinoma (NPC) post chemo-radiotherapy (CRT). Whether it is due to intrinsic (e.g., host-defense mechanisms of the epithelium), epigenetic or extrinsic factors is not fully understood. Tissue biopsies of the middle turbinate (MT) and inferior turbinate (IT) from NPC patients after CRT (mean of 3 years, n = 39) were compared with the IT biopsies from healthy subjects (n = 44). The epithelial ultrastructure was examined by transmission electron microscope (TEM). mRNA and protein expressions of epithelial stem/progenitor cells markers, as well markers of cell proliferation and differentiation markers was analyzed. Abnormal epithelial architecture was observed in all tissue samples of NPC patients. Significantly decreased expression levels of mRNA and protein levels for p63 (basal cells), Ki67 (cell proliferation), p63+/KRT5+ (epithelial stem/progenitor cells), MUC5AC and MUC5B (secretary proteins from goblet cells), alpha-tubulin, beta-tubulin and TAp73 (ciliated cells), DNAH5 and DNAI1 and RSPH4A (microtubule assemblies of motile cilia), FOXJ1 and CP110 (ciliogenesis-associated markers) were evident in MT and IT biopsies from NPC patients when compared to healthy controls. CRT causes long-term defects of epithelial barrier functions and increases the susceptibility of these patients to upper respiratory tract infection and inflammation. [ABSTRACT FROM AUTHOR]