Abstract
Identification of biomarkers for molecular classification of cancer and for differentiation between cancerous and normal epithelium remains a vital issue in the field of head and neck cancer. Here we aimed to compare the ability of proteome and lipidome components to discriminate oral cancer from normal mucosa. Tissue specimens including squamous cell cancer and normal epithelium were analyzed by MALDI mass spectrometry imaging. Two molecular domains of tissue components were imaged in serial sections—peptides (resulting from trypsin-processed proteins) and lipids (primarily zwitterionic phospholipids), then regions of interest corresponding to cancer and normal epithelium were compared. Heterogeneity of cancer regions was higher than the heterogeneity of normal epithelium, and the distribution of peptide components was more heterogeneous than the distribution of lipid components. Moreover, there were more peptide components than lipid components that showed significantly different abundance between cancer and normal epithelium (median of the Cohen’s effect was 0.49 and 0.31 in case of peptide and lipid components, respectively). Multicomponent cancer classifier was tested (vs. normal epithelium) using tissue specimens from three patients and then validated with a tissue specimen from the fourth patient. Peptide-based signature and lipid-based signature allowed cancer classification with a weighted accuracy of 0.85 and 0.69, respectively. Nevertheless, both classifiers had very high precision (0.98 and 0.94, respectively). We concluded that though molecular differences between cancerous and normal mucosa were higher in the proteome domain than in the analyzed lipidome subdomain, imaging of lipidome components also enabled discrimination of oral cancer and normal epithelium. Therefore, both cancer proteome and lipidome are promising sources of biomarkers of oral malignancies.
Highlights
Cancer located in the head and neck region is the sixth most common cancer worldwide, accounting for above 4% of cancer cases overall (Jemal et al 2011)
We revealed here that a large number of cellular proteins represented by their tryptic peptides imaged by MALDI–Mass spectrometry imaging (MSI) showed significantly different abundances between normal and cancerous mucosa
Direct comparison of protein and lipid domain between paired tissue regions corresponding to oral cancer and normal epithelium was already performed using the Raman spectroscopy
Summary
Cancer located in the head and neck region is the sixth most common cancer worldwide, accounting for above 4% of cancer cases overall (Jemal et al 2011). The generally accepted molecular biomarkers to guide management of HNSCC patient are still missing, therapeutic decisions are solely based on tumor localization and traditional staging. Since surgery is the primary treatment in most HNSCC cases, uncompleted resection of primary tumor could be a reason for treatment failure due to local recurrence. The histopathological examination is used to determine the adequacy of surgical resection of the tumor. This analysis could miss out sub-microscopic and/or pre-cancerous spots. Determination of molecular factors discriminating between cancerous and normal mucosa for proper delineation of tumor area remains another critical issue in the field of molecular diagnostics of HNSCC (de Carvalho et al 2012)
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