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Published in: BMC Cancer 1/2019

Open Access 01-12-2019 | Biomarkers | Research article

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

Authors: Dorival Mendes Rodrigues-Junior, Soon Sim Tan, Luciano de Souza Viana, Andre Lopes Carvalho, Sai Kiang Lim, N Gopalakrishna Iyer, Andre Luiz Vettore

Published in: BMC Cancer | Issue 1/2019

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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.
Appendix
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Literature
1.
go back to reference Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRef Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRef
2.
go back to reference Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer. 2013;49:1374–403.CrossRef Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer. 2013;49:1374–403.CrossRef
3.
go back to reference Argiris A, Karamouzis MV, Raben D, Ferris RL. Head and neck cancer. Lancet. 2008;371(9625):1695–709.CrossRef Argiris A, Karamouzis MV, Raben D, Ferris RL. Head and neck cancer. Lancet. 2008;371(9625):1695–709.CrossRef
4.
go back to reference Viana LS, Silva FCA, Jacome AAA, et al. Efficacy and safety of a cisplatin and paclitaxel induction regimen followed by chemoradiotherapy for patients with locally advanced head and neck squamous cell carcinoma. Head Neck. 2016;38:e970–80.CrossRef Viana LS, Silva FCA, Jacome AAA, et al. Efficacy and safety of a cisplatin and paclitaxel induction regimen followed by chemoradiotherapy for patients with locally advanced head and neck squamous cell carcinoma. Head Neck. 2016;38:e970–80.CrossRef
5.
go back to reference Iyer NG, Tan DS, Tan VK, et al. Randomized trial comparing surgery and adjuvant radiotherapy versus concurrent chemoradiotherapy in patients with advanced, nonmetastatic squamous cell carcinoma of the head and neck: 10-year update and subset analysis. Cancer. 2015;121:1599–607.CrossRef Iyer NG, Tan DS, Tan VK, et al. Randomized trial comparing surgery and adjuvant radiotherapy versus concurrent chemoradiotherapy in patients with advanced, nonmetastatic squamous cell carcinoma of the head and neck: 10-year update and subset analysis. Cancer. 2015;121:1599–607.CrossRef
6.
go back to reference Colombo M, Raposo G, Théry C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol. 2014;30:255–89.CrossRef Colombo M, Raposo G, Théry C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol. 2014;30:255–89.CrossRef
7.
go back to reference Yáñez-Mó M, Siljander PRM, Andreu Z, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 2015;4:27066.CrossRef Yáñez-Mó M, Siljander PRM, Andreu Z, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 2015;4:27066.CrossRef
8.
go back to reference Hong CS, Muller L, Whiteside TL, Boyiadzis M. Plasma exosomes as markers of therapeutic response in patients with acute myeloid leukemia. Front Immunol. 2014;5:160–9.CrossRef Hong CS, Muller L, Whiteside TL, Boyiadzis M. Plasma exosomes as markers of therapeutic response in patients with acute myeloid leukemia. Front Immunol. 2014;5:160–9.CrossRef
9.
go back to reference Tkach M, Théry C. Communication by extracellular vesicles: where we are and where we need to go. Cell. 2016;164(6):1226–32.CrossRef Tkach M, Théry C. Communication by extracellular vesicles: where we are and where we need to go. Cell. 2016;164(6):1226–32.CrossRef
10.
go back to reference Azmi AS, Bao B, Sarkar FH. Exosomes in cancer development, metastasis, and drug resistance: a comprehensive review. Cancer Metastasis Rev. 2013;32:623–42.CrossRef Azmi AS, Bao B, Sarkar FH. Exosomes in cancer development, metastasis, and drug resistance: a comprehensive review. Cancer Metastasis Rev. 2013;32:623–42.CrossRef
11.
go back to reference Principe S, Hui AB, Bruce J, et al. Tumor-derived exosomes and microvesicles in head and neck cancer: implications for tumor biology and biomarker discovery. Proteomics. 2013;13:1608–23.CrossRef Principe S, Hui AB, Bruce J, et al. Tumor-derived exosomes and microvesicles in head and neck cancer: implications for tumor biology and biomarker discovery. Proteomics. 2013;13:1608–23.CrossRef
12.
go back to reference Ramirez MI, Amorim MG, Gadelha C, et al. Technical challenges of working with extracellular vesicles. Nanoscale. 2018;10(3):881–906.CrossRef Ramirez MI, Amorim MG, Gadelha C, et al. Technical challenges of working with extracellular vesicles. Nanoscale. 2018;10(3):881–906.CrossRef
13.
go back to reference Whiteside TL. Exosomes and tumor-mediated immune suppression. J Clin Invest. 2016;126:1216–23.CrossRef Whiteside TL. Exosomes and tumor-mediated immune suppression. J Clin Invest. 2016;126:1216–23.CrossRef
14.
go back to reference Ludwig S, Floros T, Theodoraki MN, et al. Suppression of lymphocyte functions by plasma exosomes correlates with disease activity in patients with head and neck Cancer. Clin Cancer Res. 2017;23:4843–54.CrossRef Ludwig S, Floros T, Theodoraki MN, et al. Suppression of lymphocyte functions by plasma exosomes correlates with disease activity in patients with head and neck Cancer. Clin Cancer Res. 2017;23:4843–54.CrossRef
15.
go back to reference Bergmann C, Strauss L, Wang Y, et al. T regulatory type 1 cells in squamous cell carcinoma of the head and neck: mechanisms of suppression and expansion in advanced disease. Clin CancerRes. 2008;14(12):3706–15.CrossRef Bergmann C, Strauss L, Wang Y, et al. T regulatory type 1 cells in squamous cell carcinoma of the head and neck: mechanisms of suppression and expansion in advanced disease. Clin CancerRes. 2008;14(12):3706–15.CrossRef
16.
go back to reference Filipazzi P, Burdek M, Villa A, Rivoltini L, Huber V. Recent advances on the role of tumor exosomes in immunosuppression and disease progression. SeminCancerBiol. 2012;22(4):342–9. Filipazzi P, Burdek M, Villa A, Rivoltini L, Huber V. Recent advances on the role of tumor exosomes in immunosuppression and disease progression. SeminCancerBiol. 2012;22(4):342–9.
17.
go back to reference Peinado H, Aleckovic M, Lavotshkin S, et al. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. NatMed. 2012;18(6):883–91. Peinado H, Aleckovic M, Lavotshkin S, et al. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. NatMed. 2012;18(6):883–91.
18.
go back to reference Lefebvre JL, Ang KK. Larynx preservation clinical trial design: key issues and recommendations--a consensus panel summary. Head Neck. 2009;31:429–41.CrossRef Lefebvre JL, Ang KK. Larynx preservation clinical trial design: key issues and recommendations--a consensus panel summary. Head Neck. 2009;31:429–41.CrossRef
19.
go back to reference Théry C, Ostrowski M, Segura E. Membrane vesicles as conveyors of immune responses. Nat Rev Immunol. 2009;9(8):581–93.CrossRef Théry C, Ostrowski M, Segura E. Membrane vesicles as conveyors of immune responses. Nat Rev Immunol. 2009;9(8):581–93.CrossRef
20.
go back to reference Tan KH, Tan SS, Sze SK, et al. Plasma biomarker discovery in preeclampsia using a novel differential isolation technology for circulating extracellular vesicles. Am J Obstet Gynecol. 2014;211(4):380e1–e13.CrossRef Tan KH, Tan SS, Sze SK, et al. Plasma biomarker discovery in preeclampsia using a novel differential isolation technology for circulating extracellular vesicles. Am J Obstet Gynecol. 2014;211(4):380e1–e13.CrossRef
21.
go back to reference Mi H, Huang X, Muruganujan A, et al. PANTHER version 11: expanded annotation data from gene ontology and Reactome pathways, and data analysis tool enhancements. Nucleic Acids Res. 2017;45(D1):D183–9.CrossRef Mi H, Huang X, Muruganujan A, et al. PANTHER version 11: expanded annotation data from gene ontology and Reactome pathways, and data analysis tool enhancements. Nucleic Acids Res. 2017;45(D1):D183–9.CrossRef
22.
go back to reference Le QT, Sutphin PD, Raychaudhuri S, et al. Identification of osteopontin as a prognostic plasma marker for head and neck squamous cell carcinomas. Clin Cancer Res. 2003;9:59–67.PubMed Le QT, Sutphin PD, Raychaudhuri S, et al. Identification of osteopontin as a prognostic plasma marker for head and neck squamous cell carcinomas. Clin Cancer Res. 2003;9:59–67.PubMed
23.
go back to reference Gehrmann M, Specht HM, Bayer C, et al. Hsp70--a biomarker for tumor detection and monitoring of outcome of radiation therapy in patients with squamous cell carcinoma of the head and neck. Radiat Oncol. 2014;9:131–40.CrossRef Gehrmann M, Specht HM, Bayer C, et al. Hsp70--a biomarker for tumor detection and monitoring of outcome of radiation therapy in patients with squamous cell carcinoma of the head and neck. Radiat Oncol. 2014;9:131–40.CrossRef
24.
go back to reference Singh RD, Haridas N, Patel JB, et al. Matrix metalloproteinases and their inhibitors: correlation with invasion and metastasis in oral cancer. Indian J Clin Biochem. 2010;25:250–9.CrossRef Singh RD, Haridas N, Patel JB, et al. Matrix metalloproteinases and their inhibitors: correlation with invasion and metastasis in oral cancer. Indian J Clin Biochem. 2010;25:250–9.CrossRef
25.
go back to reference Lin CW, Tseng SW, Yang SF, et al. Role of lipocalin 2 and its complex with matrix metalloproteinase-9 in oral cancer. Oral Dis. 2012;18:734–40.CrossRef Lin CW, Tseng SW, Yang SF, et al. Role of lipocalin 2 and its complex with matrix metalloproteinase-9 in oral cancer. Oral Dis. 2012;18:734–40.CrossRef
26.
go back to reference Su CW, Su BF, Chiang WL, et al. Plasma levels of the tissue inhibitor matrix metalloproteinase-3 as a potential biomarker in oral cancer progression. Int J Med Sci. 2017;14:37–44.CrossRef Su CW, Su BF, Chiang WL, et al. Plasma levels of the tissue inhibitor matrix metalloproteinase-3 as a potential biomarker in oral cancer progression. Int J Med Sci. 2017;14:37–44.CrossRef
27.
go back to reference Sill M, Schröder C, Shen Y, et al. Protein profiling gastric Cancer and neighboring control tissues using high-content antibody microarrays. Microarrays (Basel). 2016;5(3). Sill M, Schröder C, Shen Y, et al. Protein profiling gastric Cancer and neighboring control tissues using high-content antibody microarrays. Microarrays (Basel). 2016;5(3).
28.
go back to reference Smith L, Watson MB, O'Kane SL, Drew PJ, Lind MJ, Cawkwell L. The analysis of doxorubicin resistance in human breast cancer cells using antibody microarrays. Mol Cancer Ther. 2006;5(8):2115–20.CrossRef Smith L, Watson MB, O'Kane SL, Drew PJ, Lind MJ, Cawkwell L. The analysis of doxorubicin resistance in human breast cancer cells using antibody microarrays. Mol Cancer Ther. 2006;5(8):2115–20.CrossRef
29.
go back to reference Sreekumar A, Nyati MK, Varambally S, et al. Profiling of cancer cells using protein microarrays: discovery of novel radiation-regulated proteins. Cancer Res. 2001;61(20):7585–93.PubMed Sreekumar A, Nyati MK, Varambally S, et al. Profiling of cancer cells using protein microarrays: discovery of novel radiation-regulated proteins. Cancer Res. 2001;61(20):7585–93.PubMed
30.
go back to reference Arantes LMRB, De Carvalho AC, Melendez ME, Lopes Carvalho A. Serum, plasma and saliva biomarkers for head and neck cancer. Expert Rev Mol Diagn. 2018;18(1):85–112.CrossRef Arantes LMRB, De Carvalho AC, Melendez ME, Lopes Carvalho A. Serum, plasma and saliva biomarkers for head and neck cancer. Expert Rev Mol Diagn. 2018;18(1):85–112.CrossRef
31.
go back to reference Zupancic K, Blejec A, Herman A, et al. Identification of plasma biomarker candidates in glioblastoma using an antibody-array-based proteomic approach. Radiol Oncol. 2014;48(3):257–66.CrossRef Zupancic K, Blejec A, Herman A, et al. Identification of plasma biomarker candidates in glioblastoma using an antibody-array-based proteomic approach. Radiol Oncol. 2014;48(3):257–66.CrossRef
32.
go back to reference Righetti PG, Castagna A, Antonucci F, et al. Proteome analysis in the clinical chemistry laboratory: myth or reality? Clin Chim Acta. 2005;357(2):123–39.CrossRef Righetti PG, Castagna A, Antonucci F, et al. Proteome analysis in the clinical chemistry laboratory: myth or reality? Clin Chim Acta. 2005;357(2):123–39.CrossRef
33.
go back to reference Diamandis EP. Mass spectrometry as a diagnostic and a cancer biomarker discovery tool: opportunities and potential limitations. Mol Cell Proteomics. 2004;3:367–78.CrossRef Diamandis EP. Mass spectrometry as a diagnostic and a cancer biomarker discovery tool: opportunities and potential limitations. Mol Cell Proteomics. 2004;3:367–78.CrossRef
34.
go back to reference Liu T, Qian WJ, Mottaz HM, et al. Evaluation of multiprotein immunoaffinity subtraction for plasma proteomics and candidate biomarker discovery using mass spectrometry. Mol Cell Proteomics. 2006;5(11):2167–74.CrossRef Liu T, Qian WJ, Mottaz HM, et al. Evaluation of multiprotein immunoaffinity subtraction for plasma proteomics and candidate biomarker discovery using mass spectrometry. Mol Cell Proteomics. 2006;5(11):2167–74.CrossRef
35.
go back to reference Patel K, Wen J, Magliocca K, et al. Heat shock protein 90 (HSP90) is overexpressed in p16-negative oropharyngeal squamous cell carcinoma, and its inhibition in vitro potentiates the effects of chemoradiation. Cancer Chemother Pharmacol. 2014;74(5):1015–22.CrossRef Patel K, Wen J, Magliocca K, et al. Heat shock protein 90 (HSP90) is overexpressed in p16-negative oropharyngeal squamous cell carcinoma, and its inhibition in vitro potentiates the effects of chemoradiation. Cancer Chemother Pharmacol. 2014;74(5):1015–22.CrossRef
36.
go back to reference Dewyer NA, Wolf GT, Light E, Worden F, Urba S, Eisbruch A, Bradford CR, Chepeha DB, Prince ME, Moyer J, Taylor J. Circulating CD4-positive lymphocyte levels as predictor of response to induction chemotherapy in patients with advanced laryngeal cancer. Head Neck. 2014;36(1):9–14.CrossRef Dewyer NA, Wolf GT, Light E, Worden F, Urba S, Eisbruch A, Bradford CR, Chepeha DB, Prince ME, Moyer J, Taylor J. Circulating CD4-positive lymphocyte levels as predictor of response to induction chemotherapy in patients with advanced laryngeal cancer. Head Neck. 2014;36(1):9–14.CrossRef
37.
go back to reference Liu M, Zhang X, Hu CF, Xu Q, Zhu HX, Xu NZ. MicroRNA-mRNA functional pairs for cisplatin resistance in ovarian cancer cells. Chin J Cancer. 2014;33(6):285–94.CrossRef Liu M, Zhang X, Hu CF, Xu Q, Zhu HX, Xu NZ. MicroRNA-mRNA functional pairs for cisplatin resistance in ovarian cancer cells. Chin J Cancer. 2014;33(6):285–94.CrossRef
38.
go back to reference Wan B, Dai L, Wang L, et al. Knockdown of BRCA2 enhances cisplatin and cisplatin-induced autophagy in ovarian cancer cells. Endocr Relat Cancer. 2018;25(1):69–82.CrossRef Wan B, Dai L, Wang L, et al. Knockdown of BRCA2 enhances cisplatin and cisplatin-induced autophagy in ovarian cancer cells. Endocr Relat Cancer. 2018;25(1):69–82.CrossRef
39.
go back to reference Nicholson RI, Gee JM, Harper ME. EGFR and cancer prognosis. Eur J Cancer. 2001;37(Suppl 4):S9–15.CrossRef Nicholson RI, Gee JM, Harper ME. EGFR and cancer prognosis. Eur J Cancer. 2001;37(Suppl 4):S9–15.CrossRef
40.
go back to reference Zhang Y, Molavi O, Su M, Lai R. The clinical and biological significance of STAT1 in esophageal squamous cell carcinoma. BMC Cancer. 2014;14:791–805.CrossRef Zhang Y, Molavi O, Su M, Lai R. The clinical and biological significance of STAT1 in esophageal squamous cell carcinoma. BMC Cancer. 2014;14:791–805.CrossRef
41.
go back to reference Azimian H, Dayyani M, Toossi MTB, Mahmoudi M. Bax/Bcl-2 expression ratio in prediction of response to breast cancer radiotherapy. Iran J Basic Med Sci. 2018;21(3):325–32.PubMedPubMedCentral Azimian H, Dayyani M, Toossi MTB, Mahmoudi M. Bax/Bcl-2 expression ratio in prediction of response to breast cancer radiotherapy. Iran J Basic Med Sci. 2018;21(3):325–32.PubMedPubMedCentral
42.
go back to reference Deep G, Jain AK, Ramteke A, et al. SNAI1 is critical for the aggressiveness of prostate cancer cells with low E-cadherin. Mol Cancer. 2014;13:37.CrossRef Deep G, Jain AK, Ramteke A, et al. SNAI1 is critical for the aggressiveness of prostate cancer cells with low E-cadherin. Mol Cancer. 2014;13:37.CrossRef
43.
go back to reference Tang X, Jin L, Cao P, et al. MicroRNA-16 sensitizes breast cancer cells to paclitaxel through suppression of IKBKB expression. Oncotarget. 2016;7(17):23668–83.PubMedPubMedCentral Tang X, Jin L, Cao P, et al. MicroRNA-16 sensitizes breast cancer cells to paclitaxel through suppression of IKBKB expression. Oncotarget. 2016;7(17):23668–83.PubMedPubMedCentral
44.
go back to reference Hsu HW, Wall NR, Hsueh CT, et al. Combination antiangiogenic therapy and radiation in head and neck cancers. Oral Oncol. 2014;50:19–26.CrossRef Hsu HW, Wall NR, Hsueh CT, et al. Combination antiangiogenic therapy and radiation in head and neck cancers. Oral Oncol. 2014;50:19–26.CrossRef
45.
go back to reference Vassilakopoulou M, Psyrri A, Argiris A. Targeting angiogenesis in head and neck cancer. Oral Oncol. 2015;51(5):409–15.CrossRef Vassilakopoulou M, Psyrri A, Argiris A. Targeting angiogenesis in head and neck cancer. Oral Oncol. 2015;51(5):409–15.CrossRef
46.
go back to reference Bauer JA, Trask DK, Kumar B, Los G, Castro J, Lee JS, Chen J, Wang S, Bradford CR, Carey TE. Reversal of cisplatin resistance with a BH3 mimetic, (−)-gossypol, in head and neck cancer cells: role of wild-type p53 and Bcl-xL. Mol Cancer Ther. 2005;4(7):1096–104.CrossRef Bauer JA, Trask DK, Kumar B, Los G, Castro J, Lee JS, Chen J, Wang S, Bradford CR, Carey TE. Reversal of cisplatin resistance with a BH3 mimetic, (−)-gossypol, in head and neck cancer cells: role of wild-type p53 and Bcl-xL. Mol Cancer Ther. 2005;4(7):1096–104.CrossRef
47.
go back to reference Ji X, Jiang C, Liu Y, Bu D, Xiao S. Fas ligand gene transfer effectively induces apoptosis in head and neck cancer cells. Acta Otolaryngol. 2011;131(8):876–81.CrossRef Ji X, Jiang C, Liu Y, Bu D, Xiao S. Fas ligand gene transfer effectively induces apoptosis in head and neck cancer cells. Acta Otolaryngol. 2011;131(8):876–81.CrossRef
48.
go back to reference Gadhikar MA, Sciuto MR, Alves MV, et al. Chk1/2 inhibition overcomes the cisplatin resistance of head and neck cancer cells secondary to the loss of functional p53. Mol Cancer Ther. 2013;12(9):1860–73.CrossRef Gadhikar MA, Sciuto MR, Alves MV, et al. Chk1/2 inhibition overcomes the cisplatin resistance of head and neck cancer cells secondary to the loss of functional p53. Mol Cancer Ther. 2013;12(9):1860–73.CrossRef
Metadata
Title
A preliminary investigation of circulating extracellular vesicles and biomarker discovery associated with treatment response in head and neck squamous cell carcinoma
Authors
Dorival Mendes Rodrigues-Junior
Soon Sim Tan
Luciano de Souza Viana
Andre Lopes Carvalho
Sai Kiang Lim
N Gopalakrishna Iyer
Andre Luiz Vettore
Publication date
01-12-2019
Publisher
BioMed Central
Keyword
Biomarkers
Published in
BMC Cancer / Issue 1/2019
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-019-5565-9

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