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. 2019 Apr 23;19(1):373.
doi: 10.1186/s12885-019-5565-9.

A preliminary investigation of circulating extracellular vesicles and biomarker discovery associated with treatment response in head and neck squamous cell carcinoma

Dorival Mendes Rodrigues-Junior  1   2 , Soon Sim Tan  3 , Luciano de Souza Viana  4 , Andre Lopes Carvalho  4 , Sai Kiang Lim  3 , N Gopalakrishna Iyer  5   6 , Andre Luiz Vettore  7
Affiliations

A preliminary investigation of circulating extracellular vesicles and biomarker discovery associated with treatment response in head and neck squamous cell carcinoma

Dorival Mendes Rodrigues-Junior et al. BMC Cancer. .

Abstract

Background: 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.

Methods: In 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.

Results: Of 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.

Conclusion: This 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.

Keywords: Biomarker discovery; Chemoradiation therapy; Extracellular vesicles; HNSCC; Head and neck squamous cell carcinoma; Treatment response.

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Conflict of interest statement

Ethics approval and consent to participate

Written informed consent was obtained from all HNSCC patients. This study was approved by the institution ethics committees (CEP-UNIFESP: 1610/2016 and CEP-HCBarretos: 231/2009).

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Distribution of specific proteins in the CTB-EVs, AV-EVs and crude plasma detected through Antibody Array assays. The comparison of the protein content in CTB-EVs, AV-EVs and crude plasma from pooled 6 complete responder (CR) patients and 6 non-responder (NR) patients revealed 119 proteins specific to the NR patients, while 38 proteins were specific to the CR patients. The level of protein detected was normalized by the mean of positive controls present in the antibody array assay (Full Moon Biosystems)
Fig. 2
Fig. 2
Relative abundances of the putative HNSCC protein biomarkers for CRT treatment response in the pooled plasma samples analyzed. Among the specific proteins detected in each subpopulation (CTB-EVs, AV-EVs and crude plasma), the top 10 most abundant ones in patients with complete response to CRT (CR; a, b and c) or from the non-responders (Nr; d, e and f) are presented
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