Characterizing the Epithelial-mesenchymal Transition Status of Circulating Tumor Cells in Head and Neck Squamous Cell Carcinoma

Overview

Journal Head Neck

Specialties General Surgery
Oncology

Date 2022 Aug 5

PMID 35932094

Authors

Karl Payne

Jill Brooks

Nikolaos Batis

Graham Taylor

Paul Nankivell

Hisham Mehanna

Affiliations

Soon will be listed here.

Abstract

Background: Circulating tumor cells (CTCs), in particular those undergoing an epithelial-mesenchymal transition (EMT), are a promising source of biomarkers in head and neck squamous cell carcinoma (HNSCC). Our aim was to validate a protocol using microfluidic enrichment (Parsortix platform) with flow-cytometry CTC characterization.

Method: Blood samples from 20 treatment naïve HNSCC patients underwent Parsortix enrichment and flow cytometry analysis to quantify CTCs and identify epithelial or EMT subgroups-correlated to clinical outcomes and EMT gene-expression in tumor tissue.

Results: CTCs were detected in 65% of patients (mean count 4 CTCs/ml). CTCs correlated with advanced disease (p = 0.0121), but not T or N classification. Epithelial or EMT CTCs did not correlate with progression-free or overall survival. Tumor mesenchymal gene-expression did not correlate with CTC EMT expression (p = 0.347).

Discussion: Microfluidic enrichment and flow cytometry successfully characterizes EMT CTCs in HNSCC. The lack of association between tumor and CTC EMT profile suggests CTCs may undergo an adaptive EMT in response to stimuli within the circulation.

Citing Articles

Feasibility of mass cytometry proteomic characterisation of circulating tumour cells in head and neck squamous cell carcinoma for deep phenotyping.

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Protocol for tumor dissociation and fluorescence-activated cell sorting of human head and neck cancers.

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Diagnostic Predictors of Immunotherapy Response in Head and Neck Squamous Cell Carcinoma.

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PMID: 36900006 PMC: 10001329. DOI: 10.3390/diagnostics13050862.

Characterizing the epithelial-mesenchymal transition status of circulating tumor cells in head and neck squamous cell carcinoma.

Payne K, Brooks J, Batis N, Taylor G, Nankivell P, Mehanna H Head Neck. 2022; 44(11):2545-2554.

PMID: 35932094 PMC: 9804280. DOI: 10.1002/hed.27167.

References

Lampignano R, Yang L, Neumann M, Franken A, Fehm T, Niederacher D . A Novel Workflow to Enrich and Isolate Patient-Matched EpCAM and EpCAM CTCs Enables the Comparative Characterization of the PIK3CA Status in Metastatic Breast Cancer. Int J Mol Sci. 2017; 18(9). PMC: 5618534. DOI: 10.3390/ijms18091885. View

Payne K, Pugh M, Brooks J, Batis N, Taylor G, Nankivell P . Circulating Tumour Cell Expression of Immune Markers as Prognostic and Therapeutic Biomarkers in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis. Int J Mol Sci. 2020; 21(21). PMC: 7662307. DOI: 10.3390/ijms21218229. View

Smith A, Teknos T, Pan Q . Epithelial to mesenchymal transition in head and neck squamous cell carcinoma. Oral Oncol. 2012; 49(4):287-92. PMC: 3586749. DOI: 10.1016/j.oraloncology.2012.10.009. View

Bhatia S, Wang P, Toh A, Thompson E . New Insights Into the Role of Phenotypic Plasticity and EMT in Driving Cancer Progression. Front Mol Biosci. 2020; 7:71. PMC: 7190792. DOI: 10.3389/fmolb.2020.00071. View

Thiery J . Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer. 2002; 2(6):442-54. DOI: 10.1038/nrc822. View

Dobin A, Davis C, Schlesinger F, Drenkow J, Zaleski C, Jha S . STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2012; 29(1):15-21. PMC: 3530905. DOI: 10.1093/bioinformatics/bts635. View

Bhan I, Mosesso K, Goyal L, Philipp J, Kalinich M, Franses J . Detection and Analysis of Circulating Epithelial Cells in Liquid Biopsies From Patients With Liver Disease. Gastroenterology. 2018; 155(6):2016-2018.e11. PMC: 6347478. DOI: 10.1053/j.gastro.2018.09.020. View

Pantel K, Deneve E, Nocca D, Coffy A, Vendrell J, Maudelonde T . Circulating epithelial cells in patients with benign colon diseases. Clin Chem. 2011; 58(5):936-40. DOI: 10.1373/clinchem.2011.175570. View

Chen Y, Li S, Li W, Yang R, Zhang X, Ye Y . Circulating tumor cells undergoing EMT are poorly correlated with clinical stages or predictive of recurrence in hepatocellular carcinoma. Sci Rep. 2019; 9(1):7084. PMC: 6506548. DOI: 10.1038/s41598-019-43572-1. View

10.

Ring A, Mineyev N, Zhu W, Park E, Lomas C, Punj V . EpCAM based capture detects and recovers circulating tumor cells from all subtypes of breast cancer except claudin-low. Oncotarget. 2015; 6(42):44623-34. PMC: 4792580. DOI: 10.18632/oncotarget.5977. View

11.

Savagner P . The epithelial-mesenchymal transition (EMT) phenomenon. Ann Oncol. 2010; 21 Suppl 7:vii89-92. PMC: 3379967. DOI: 10.1093/annonc/mdq292. View

12.

Love M, Huber W, Anders S . Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014; 15(12):550. PMC: 4302049. DOI: 10.1186/s13059-014-0550-8. View

13.

Hristozova T, Konschak R, Stromberger C, Fusi A, Liu Z, Weichert W . The presence of circulating tumor cells (CTCs) correlates with lymph node metastasis in nonresectable squamous cell carcinoma of the head and neck region (SCCHN). Ann Oncol. 2011; 22(8):1878-85. DOI: 10.1093/annonc/mdr130. View

14.

Payne K, Brooks J, Taylor G, Batis N, Noyvert B, Pan Y . Immediate Sample Fixation Increases Circulating Tumour Cell (CTC) Capture and Preserves Phenotype in Head and Neck Squamous Cell Carcinoma: Towards a Standardised Approach to Microfluidic CTC Biomarker Discovery. Cancers (Basel). 2021; 13(21). PMC: 8583049. DOI: 10.3390/cancers13215519. View

15.

Hsieh J, Lin H, Huang C, Hsu H, Wu T, Lee C . Prognostic value of circulating tumor cells with podoplanin expression in patients with locally advanced or metastatic head and neck squamous cell carcinoma. Head Neck. 2014; 37(10):1448-55. DOI: 10.1002/hed.23779. View

16.

Rossi E, Zamarchi R . Single-Cell Analysis of Circulating Tumor Cells: How Far Have We Come in the -Omics Era?. Front Genet. 2019; 10:958. PMC: 6811661. DOI: 10.3389/fgene.2019.00958. View

17.

Payne K, Brooks J, Spruce R, Batis N, Taylor G, Nankivell P . Circulating Tumour Cell Biomarkers in Head and Neck Cancer: Current Progress and Future Prospects. Cancers (Basel). 2019; 11(8). PMC: 6721520. DOI: 10.3390/cancers11081115. View

18.

McMullen K, Chalmers J, Lang J, Kumar P, Jatana K . Circulating tumor cells in head and neck cancer: A review. World J Otorhinolaryngol Head Neck Surg. 2017; 2(2):109-116. PMC: 5698518. DOI: 10.1016/j.wjorl.2016.05.003. View

19.

Dong Y, Skelley A, Merdek K, Sprott K, Jiang C, Pierceall W . Microfluidics and circulating tumor cells. J Mol Diagn. 2012; 15(2):149-57. DOI: 10.1016/j.jmoldx.2012.09.004. View

20.

Lallo A, Schenk M, Frese K, Blackhall F, Dive C . Circulating tumor cells and CDX models as a tool for preclinical drug development. Transl Lung Cancer Res. 2017; 6(4):397-408. PMC: 5583071. DOI: 10.21037/tlcr.2017.08.01. View