Study highlights importance of biomarkers in tumour progression

The University of Birmingham has published the results of a study undertaken in head and neck squamous cell carcinoma (HNSCC) by liquid biopsy company ANGLE, which characterised the epithelial-mesenchymal transition (EMT) status of circulating tumour cells (CTCs).  

EMT is clinically significant due to its role in tumour progression and invasion, the development of metastasis, metabolic reprogramming, immune evasion, and resistance of cancer cells to therapy. 

The study used the Parsortix system to harvest CTCs from peripheral blood samples from 20 treatment-naïve HNSCC patients at baseline prior to surgery. The researchers performed flow-cytometry EMT characterisation of CTCs as compared to EMT gene expression in tumour tissue and investigated expression correlation with respect to clinical outcomes. The expression of EpCAM and N-cadherin were utilised to characterise CTC status as epithelial or EMT. CTCs were detected in 65% of patients and 77% of positive samples included CTCs undergoing EMT. 

The research demonstrated that EMT status of CTCs was almost exclusively associated with advanced stage (III-IV) disease. In this small patient cohort CTC enumeration alone was not reported to be prognostic with respect to overall survival and progression free survival. However, CTC EMT status was found to be independent to that of tumour tissue, highlighting the potential clinical utility of CTC EMT biomarkers as a complementary analyte to tumour tissue biopsy or as therapeutic targets. 

Head and neck cancer (HNC) is a broad term used to group oral cavity, pharynx, larynx, salivary gland and nose and sinus cancer, with 90-95% of HNCs being squamous cell cancers. Globally, HNC accounted for over 930,000 new cases and over 460,000 deaths in 2020. In head and neck squamous cell carcinoma, 5-year survival rates are in the region of 50%, depending on cancer type and stage, but largely static for several decades. Common risk factors of this cancer include gender, ethnicity, age, poor oral hygiene, tobacco and alcohol use. The toxicity associated with current treatment regimens for this cancer results in a significant impact upon quality of life. Therefore, early diagnosis and effective targeted treatment options are urgently required to improve patient outcomes. A liquid biopsy, in particular analysing CTCs, is one potential avenue to define such therapeutic biomarkers. 

Professor Hisham Mehanna, the Chair of Head and Neck Surgery, and Director of the Institute of Head and Neck Studies and Education (InHANSE) at the Institute of Cancer and Genomic Sciences, University of Birmingham, said: “The successful characterisation of EMT CTCs in HNSCC sheds light on the potential adaptive EMT response to stimuli within the circulation of blood, providing an important and unique insight into metastasis. Prospective clinical trials are needed to answer the question regarding the predictive utility of a CTC liquid biopsy (for example CTC immune checkpoint expression directing personalised treatment), especially in recurrent/metastatic patients not amenable to repeat tissue biopsies.” 

Andrew Newland, ANGLE Founder and Chief Executive, said: “ANGLE is pleased to report on the use of the Parsortix system as a tool for HNSCC EMT classification. Evidence continues to grow supporting the potential clinical utility of CTC enrichment to provide clinical information beyond the scope of tissue biopsy. This research provides further evidence for the role that EMT CTCs play in the metastatic cascade and the clinical importance of biomarker independent CTC isolation methods which capture all subsets of CTCs. In drug discovery, this may enable the identification of drugs that are better able to target cancer cells known to be the precursors of metastasis. As metastasis is responsible for 90% of cancer deaths, this could be transformative for cancer care and patient outlook.” 

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