Abstract
BackgroundThere is a paucity of plasma-based biomarkers that prospectively segregate the outcome of patients with head and neck squamous-cell carcinoma (HNSCC) treated with chemoradiation therapy (CRT). Plasma extracellular vesicles (EVs) might be an alternative source for discovery of new specific markers present in patients with HNSCC, which could help to re-direct patients to appropriate curative therapies without delay.MethodsIn order to identify new markers in plasma compartments, Cholerae toxin B chain (CTB) and Annexin V (AV) were used to isolate EVs from pooled plasma samples from patients with locally advanced HNSCC who responded (CR, n = 6) or presented incomplete response (NR, n = 6) to CRT. The crude plasma and EVs cargo were screened by antibody array.ResultsOf the 370 polypeptides detected, 119 proteins were specific to NR patients while 38 were exclusive of the CR subjects. The Gene Set Enrichment Analysis (GSEA) and Search Tool for the Retrieval of Interacting Genes (STRING) database analysis indicated that the content of circulating plasma EVs might have a relevant function for the tumor intercellular communication in the HNSCC patients.ConclusionThis study provides a list of potential markers present in plasma compartments that might contribute to the development of tools for prediction and assessment of CRT response and potentially guide therapeutic decisions in this context.
Highlights
There is a paucity of plasma-based biomarkers that prospectively segregate the outcome of patients with head and neck squamous-cell carcinoma (HNSCC) treated with chemoradiation therapy (CRT)
Here we propose the use of antibody arrays to identify and quantify proteins carried by extracellular vesicles (EVs) circulating in the plasma of HNSCC patients that do not respond to CRT (NR, Non-Responders), and compared this profile with patients that present a complete response to this treatment (CR, Complete-Responders)
In summary, we have identified biomarker candidates present in plasma EVs or crude plasma that could stratify HNSCC patients according to their response to CRT
Summary
There is a paucity of plasma-based biomarkers that prospectively segregate the outcome of patients with head and neck squamous-cell carcinoma (HNSCC) treated with chemoradiation therapy (CRT). Plasma extracellular vesicles (EVs) might be an alternative source for discovery of new specific markers present in patients with HNSCC, which could help to re-direct patients to appropriate curative therapies without delay. 30–50% of patients with locally advanced disease survive more than 5 years, and this has not changed over the past 40 years [3]. In this context, concurrent chemoradiation therapy (CRT), with or without induction chemotherapy (IC), has emerged as the new paradigm of treatment for patients with locally advanced HNSCC affecting the oropharynx, larynx and hypopharynx [4]. It is generally believed that personalized treatment decisions based in non-invasive biomarkers able to stratify patients according to treatment response would help to optimize appropriate patient-specific therapeutic interventions, quality of life and outcomes
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