Low levels of miR-34c in nasal washings as a candidate marker of aggressive disease in wood and leather exposed workers with sinonasal intestinal-type adenocarcinomas (ITACs)

Abstract

Introduction: Sinonasal intestinal-type adenocarcinomas (ITACs) are rare and aggressive tumors, closely related to professional exposure to wood dusts or leather. Here we explored the role of non-coding RNAs controlling MUC2 in liquid biopsies and tumors from ITAC patients with the aim of identifying biomarkers and molecular mechanisms to improve early diagnosis, prognosis, and therapeutic approaches for this rare cancer. Methods: MiR-34c-3p, lncRNA AF147447 and MUC2 were measured in tumors and normal mucosa, in nasal washings (NW) from the affected and non-affected nostril and in plasma from 17 ITAC patients. The Apparent Diffusion Coefficient (ADC) was also evaluated by Magnetic Resonance Imaging. Results: MiR-34c was higher in ITACs compared to the corresponding normal mucosa (p = 0.021). Differentiated tumors exhibited higher miR-34c levels (p = 0.025) and lower ADC values (p<0.001) compared to mucinous ones and these parameters were also inversely correlated (r = 0.87; p = 0.001). High MUC2 tumor expression was associated with orbital extension (p = 0.010). Low miR-34c levels in NW were associated with orbital (p = 0.009) and intracranial (p = 0.031) extension and with advanced TNM stage (p = 0.054). Functional analysis identified Wnt, Focal adhesion, MAPK and inflammatory signalings among the pathways most enriched in mir-34c targets. Discussion: Our results suggest measuring miR-34c in NW as a biomarker for early diagnosis and monitoring of ITAC patients and for the surveillance of wood and leather exposed workers. Further research on the involvement of miR-34c regulated pathways in ITAC tumorigenesis may also allow the development of new therapeutic approaches for this rare cancer.

Keywords

• Intestinal-type sinonasal adenocarcinomas
• ITAC
• MicroRNA
• Noncoding RNA
• Biomarkers