Protein Cargo of Salivary Small Extracellular Vesicles as Potential Functional Signature of Oral Squamous Cell Carcinoma

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.

Diagnostic delay of oral squamous cell carcinoma and the fear of diagnosis: A scoping review

“…With only 4 papers describing the TNM stage, most of the patients were in the late stages of OSCC (505/694; 72.8%; Seoane-Romero et al, 2012 ; Joshi et al, 2014 ; Rutkowska et al, 2020 ; Thomas et al, 2021 ). This datum confirms that more than 50% of patients with OSCC are diagnosed at an advanced stage ( La Vecchia et al, 2004 ; Goy et al, 2009 ; Gatta et al, 2015 ; Gigliotti et al, 2019 ; Fontana et al, 2021 ).…”

Clinical applications of liquid biopsy in HPV‐negative and HPV‐positive head and neck squamous cell carcinoma: advances and challenges

“…EV-associated proteins from plasma were evaluated and revealed 43 candidate proteins with altered abundance by comparing non-cancer controls, and oral tongue squamous cell carcinoma with and without lymph node involvement [ 104 ]. Regarding saliva, Fontana et al [ 105 ] analyzed protein cargo from salivary small EVs of OSCC patients and identified differentially modulated proteins between groups. The results showed that 235 proteins were differentially modulated between OSCC-free and OSCC without lymph node metastasis (OSCC_NLNM); 157 proteins between OSCC-free and OSCC with lymph node metastasis (OSCC_LNM); 189 proteins between OSCC_NLNM and OSCC_LNM, suggesting that protein cargo from salivary EVs exhibits functional signature according to clinical conditions.…”

Extracellular Vesicle-Based Method for Detecting MYCN Amplification Status of Pediatric Neuroblastoma

“…Apoptotic-derived EVs or apoptotic bodies (>1000 nm in diameter) are generated from plasma membrane blebbing during cell apoptosis [ 18 , 19 , 20 ]. Exo and MVs are the main focus of the EV-based method development for several cancers, i.e., head and neck [ 16 ], brain [ 21 ], lung [ 22 ], colon [ 23 ], bladder [ 24 ], endometrial [ 25 ], ovarian [ 26 ] and prostate [ 27 ]. To the best of our knowledge, the EV-based method has never been developed for detecting the MYCN status of pediatric NB.…”