engleski

A proteomic approach to unravel molecular alterations underlying laryngeal cancer

Laryngeal cancer is the most common neoplasm of the upper aerodigestive tract, whose incidence is closely correlated with tobacco and alcohol consumption. Molecular mechanisms associated with pathogenesis and progression of laryngeal cancer are not fully elucidated accounting for low survival rates as the consequence of late diagnosis and inefficient treatment. Although multiple protein species with potential biomedical significance were detected in plasma and tissues from laryngeal carcinoma patients, none of them have been implemented yet into clinical practice as valid diagnostic biomarkers for monitoring disease progression and prediction of treatment response. Identification of novel molecular and cellular determinants of laryngeal carcinogenesis will open avenues for new, more effective therapies. . In the present study, we investigated global proteome profiles of tumour tissues from patients with metastatic laryngeal cancer versus patient-matched, histologically normal tissues. Importantly, we applied novel, mass spectrometry-based approach to analyse the glycan composition of tissue samples, and found that tumour tissues had lower number of glycan signals in comparison with unaffected tissues, as inferred from the ratio of product ions of N-acetyl-hexosamines (HexNAc), sialic acid (NeuAc (-H2O)) and hexose-N-acetyl-hexosamine(HexHexNAc) in HCD spectra. Although preliminary, these results indicate that aberrant glycosylation might, at least partially, account for development and progression of laryngeal cancer. Furthermore, obtained data revealed 21 and 7 up- and down-regulated proteins, respectively, in tumour tissues that play important roles in diverse cellular processes including nucleo-cytoplasmic transport, protein biosynthesis and degradation, cytokine signalling, mRNA processing and splicing, remodelling of extracellular matrix, regulation of actin cytoskeleton structure and dynamics, immune response (T- and B-cell antigen receptor signalling ; proliferation and differentiation of preactivated B-lymphocytes), cell-cell adhesion, control of cell proliferation and cellular aging, calcium homeostasis and signalling, drug resistance, regulation of transcription, iron metabolism and transport, blood coagulation and cellular metabolism. In addition to confirming the alterations in the expression level of proteins shown previously to correlate with head and neck cancer progression such as esophagin, filamin B and gelsolin, we also identified several proteins that are novel to laryngeal cancer pathogenesis including heterogeneous nuclear ribonucleoproteins R and Q, receptor-type tyrosine-protein phosphatase C, plastin-3, mortalin and hepatoma-derived growth factor 2. Functional roles of these newly identified proteins in laryngeal cancer and their diagnostic potentials have yet to be established.

mass spectrometry; glycoproteins; larynx cancer; biomarker profiling

nije evidentirano