Proteomic Analysis of Circulating Extracellular Vesicles Identifies Potential Biomarkers for Lymph Node Metastasis in Oral Tongue Squamous Cell Carcinoma

Abstract

Lymph node metastasis is the most reliable indicator of a poor prognosis for patients with oral tongue cancers. Currently, there are no biomarkers to predict whether a cancer will spread in the future if it has not already spread at the time of diagnosis. The aim of this study was to quantitatively profile the proteomes of extracellular vesicles (EVs) isolated from blood samples taken from patients with oral tongue squamous cell carcinoma with and without lymph node involvement and non-cancer controls. EVs were enriched using size exclusion chromatography (SEC) from pooled plasma samples of patients with non-nodal and nodal oral tongue squamous cell carcinoma (OTSCC) and non-cancer controls. Protein cargo was quantitatively profiled using isobaric labelling (iTRAQ) and two-dimensional high-performance liquid chromatography followed by tandem mass spectrometry. We identified 208 EV associated proteins and, after filtering, generated a short list of 136 proteins. Over 85% of the EV-associated proteins were associated with the GO cellular compartment term “extracellular exosome”. Comparisons between non-cancer controls and oral tongue squamous cell carcinoma with and without lymph node involvement revealed 43 unique candidate EV-associated proteins with deregulated expression patterns. The shortlisted EV associated proteins described here may be useful discriminatory biomarkers for differentiating OTSCC with and without nodal disease or non-cancer controls.

Extracellular Vesicles Produced by the Cardiac Microenvironment Carry Functional Enzymes to Produce Lipid Mediators In Situ

“…Moreover, it opens their potential circulating monitoring role. This hypothesis now must be explored, integrating the ability of these nanovesicles to deliver their cargo in cells or even in the surroundings, as was proposed recently for tongue cancer, where many deregulated EV proteins are found in the plasma from patients [ 44 ].…”

Circulating galectin-3 promotes tumor-endothelium-adhesion by upregulating ICAM-1 in endothelium-derived extracellular vesicles

“…As EVs has been reported to involve in tumor progression ( Goričar et al, 2021 ; Wu et al, 2021 ; Thakur et al, 2022 ), the detection of EVs as diagnostic and diagnostic biomarkers of tumor ( Thakur et al, 2020a ; Qu et al, 2021 ; Xu et al, 2021 )and EVs based drug delivery systems ( Thakur et al, 2020b ; Gaurav et al, 2021 ) has attracted extensive attention. Further research on its regulatory effects on tumor metastasis and underlying mechanism will be beneficial to its clinical application.…”

“…In the study, we noticed that galectin-3 could reduce the secretion of EVs which is quantified by the total protein expression in H-EVs and the expression of ICAM-1 in EVs. The protein expression in EVs is closely related to tumor development ( Qu et al, 2021 ). ICAM-1 is an adhesion protein expressed on the surface of endothelial cells, monocytes, lymphocytes and tumor cells ( Ramos et al, 2014 ).…”

Liquid Biopsy for Oral Cancer Diagnosis: Recent Advances and Challenges

“…Patients with high miR-503-3p had higher rates of lymph node metastasis ( p = 0.043) and had a poor pathological response to preoperative CRT ( p = 0.003) [ 26 ]. Qu et al performed proteome analysis by quantitative profiling using isobaric labelling (iTRAQ) and identified 43 EV-associated proteins related to lymph node metastasis of OSCC [ 75 ]. They also showed that expression of these candidates, including myosin-9, agrin, integrin alpha-3, actin, and serum paraoxonase/arylesterase 1, was associated with shorter overall survival in OSCC patients.…”