Abstract

The early diagnosis of oral squamous cell carcinoma (OSCC) is still an investigative challenge. Saliva has been proposed as an ideal diagnostic medium for biomarker detection by mean of liquid biopsy technique. The aim of this pilot study was to apply proteomic and bioinformatic strategies to determine the potential use of saliva small extracellular vesicles (S/SEVs) as a potential tumor biomarker source. Among the twenty-three enrolled patients, 5 were free from diseases (OSCC_FREE), 6 were with OSCC without lymph node metastasis (OSCC_NLNM), and 12 were with OSCC and lymph node metastasis (OSCC_LNM). The S/SEVs from patients of each group were pooled and properly characterized before performing their quantitative proteome comparison based on the SWATH_MS (Sequential Window Acquisition of all Theoretical Mass Spectra) method. The analysis resulted in quantitative information for 365 proteins differentially characterizing the S/SEVs of analyzed clinical conditions. Bioinformatic analysis of the proteomic data highlighted that each S/SEV group was associated with a specific cluster of enriched functional network terms. Our results highlighted that protein cargo of salivary small extracellular vesicles defines a functional signature, thus having potential value as novel predict biomarkers for OSCC.

Highlights

  • Oral squamous cell carcinoma (OSCC) is one of the most prevalent histotypes of cancer worldwide and is a challenge to public health

  • Liquid biopsy is a promising method for early diagnosis and real-time monitoring based on the analysis of circulating tumor cells (CTCs), circulating tumor DNAs, circulating cell-free microRNAs, extracellular vesicles (EVs), and other cancer-derived products isolated by the blood or other biofluids [5,6,7,8]

  • Since it is known that the protein cargo of EVs often reflects that of the originating cells, the functional signature characterizing the three clusters can probably mirror the biological status and activities of the oral mucosa cells in the three analyzed clinical conditions

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Summary

Introduction

Oral squamous cell carcinoma (OSCC) is one of the most prevalent histotypes of cancer worldwide and is a challenge to public health. More recent research has been focusing on the identification of non-invasive or minimally invasive markers for OSCC screening and longitudinal monitoring of the patients’ response to treatment. In this context, liquid biopsy is a promising method for early diagnosis and real-time monitoring based on the analysis of circulating tumor cells (CTCs), circulating tumor DNAs (ctDNAs), circulating cell-free microRNAs (cfmiRNAs), extracellular vesicles (EVs), and other cancer-derived products isolated by the blood or other biofluids (e.g., saliva, urine, ascites, pleural effusion, etc.) [5,6,7,8]. Several studies have been focused on describing the use of EV-based liquid biopsy as a source of biomarkers for several kinds of cancer [11,12,13,14]

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