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.
Highlights
It is estimated that ~380,000 people were diagnosed and ~180,000 died from oral cancer worldwide in 2020 [1]
Neck lymph node positivity in oral tongue squamous cell carcinoma (OTSCC) correlates with poor prognosis but is difficult to predict
This study has identified several potential novel, non-invasive candidate biomarkers in plasma
Summary
It is estimated that ~380,000 people were diagnosed and ~180,000 died from oral cancer worldwide in 2020 [1]. For oral tongue squamous cell carcinoma (OTSCC), earlystaged OTSCC has a better survival, with stage I disease having an 80% five-year overall survival rate as opposed to 15% for stage IV disease [2]. These types of cancers are routinely discovered at an advanced stage as they can develop without producing pain or symptoms and are associated with a poor prognosis. Advanced disease characterized by metastatic nodal involvement is the only reliable clinical indicator of poor prognosis for patients with OTSCC. The need for better biomarkers and an improved understanding of the mechanisms governing oral cancer progression is paramount to realize more robust therapeutic strategies
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