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A Rapid qPCR Test for Oral Cancer
Who invented qMIDS?
Who invented qMIDS?
Muy-Teck Teh pursued his Biomedical Science degree (B.Sc. Hons, 1996) followed by PhD in Physiology (2000) at King’s College London. Following two postdoctoral training positions funded by Wellcome Trust and Cancer Research UK, he is currently a Professor of Molecular Oral Oncology at the Barts & the London School of Medicine & Dentistry, Queen Mary University of London, leading a transnational research group investigating cancer biomarker discovery, molecular diagnostics and prognostics. He aims to translate basic science into clinical applications and towards personalised medicine based on molecular signatures. Prof Teh has international collaborators from USA, Norway, Switzerland, India, Pakistan, Sri Lanka, Malaysia and China on clinical translation of the world’s first FOXM1-based digital squamous cancer test – “qMIDS” for quantitative cancer diagnosis and prognosis. A second generation qMIDSV2 with significantly improved performance, validated in over 535 patients from UK, China and India, has been shown to be able to detect high-risk oral lesions.
Current Research
Current Research
Prof Teh identified and delineated the mechanism of a key driver oncogene FOXM1 in human cancer1-11 which subsequently led to the Molecule of the Year 2010 Award12. He later pioneered the world first FOXM1-based digital molecular cancer test - "quantitative malignancy diagnostic system (qMIDS)" for early detection oral cancer risk21. The qMIDS test has been validated on several hundreds of oral cancer patients from UK, Norway, China and India with highly accurate results (>90%) compared to conventional histopathology13,14,21. The qMIDS test requires only a tiny 1 mm (a grain of rice) tissue biopsy and test results could be obtained within 90 mins by measuring 16 genes to produce a malignancy index via an algorithm13. The qMIDS test may potentially revolutionise oral cancer diagnosis in the future by providing a cost-effective, fully automated, high-throughput, rapid, quantitative, digital diagnostic system for managing ever increasing population of patients with oral lesions. Rapid segregation and release of majority (>90%) of low risk patients from surveillance whilst channelling funding and resources to treat high-risk patients will result in long-term benefits for both the patients and healthcare establishments.
Lay articles of Prof Teh's qMIDS research:
Animated video summary [YouTube] [Chinese subtitled version 中文字幕版]
Executive research summary on Scientia (21 Oct 2020): [webpage] [PDF]
Profile article on Open Access Government (13 Nov 2020): [webpage]
A brief overview of Prof Teh's other research areas:
Identification of exosome biomarkers for developing non-invasive salivary or blood-based diagnostic tests15.
New molecular signatures were found to characterise a clinically distinct UK population of oral cancer patients that may be predisposed to therapeutic resistance16.
Using a three-dimensional (3D) culture and xenograft tumour models, a novel mechanism regulated by FOXM1 was found to promote aberrant differentiation in squamous differentiation17.
He further discovered the squamous differentiation mechanism could be perturbed by serum lipids, retinoic acid and phenol red, raised important issues with using cell culture models18.
Using in vitro and in vivo mouse models, a new target tumour suppressor gene RASSF1A was found to be regulated via a YAP pathway in nasopharyngeal carcinoma cells19.
Tobacco is a risk factor for oral cancer, recent discovery using a zebrafish model identified a genetic locus (Slit3) regulates nicotine addiction in human20 could lead to new ways to prevent or treat tobacco addiction thereby eliminating a key risk factor for many cancers including oral cancer.
Role and mechanism of vimentin in cancer metastasis22,23,24.
Receptors for SARS-CoV-2 entry in oral mucosa and OSCC25.
Mouthwashes on salivary SARS-CoV-2 viral load randomised controlled pilot study26.
Identification of two multidrug chemoresistant genes (NEK2 and INHBA) and found a naturally occurring fungal derivative Sirodesmin A and a licensed anticancer drug Carfilzomib, both targeting NEK2 and INHBA, could re-sensitise resistant HNSCC cells to cisplatin27.
Molecular Pattern Recognition
in Pre-Cancer Cells
Molecular Pattern Recognition
in Pre-Cancer Cells
All cellular processes are tightly regulated by a complex network of interacting biomolecules. Given that mRNA transcription precedes protein translation, change in gene expression levels often precedes visible pathological manifestation. Hence, transcriptome instability in the form of gene expression alterations serves as key signals for subsequent disease initiation and manifestation. Prof Teh hypothesised that if we could recognise and measure cancer-associated transcriptome instability, this could enable better understanding of cancer initiation and smarter way to predict cancer risk13,14 in otherwise asymptomatic patients7-9. With the help of Artificial Intelligence (AI), this study could be translated into a clinically useful clinical AI tool for risk prediction before disease manifestation.
Molecular Patterns of Therapeutic Resistance
in Cancer Cells
Molecular Patterns of Therapeutic Resistance
in Cancer Cells
Multidrug resistance renders chemotherapeutic treatment failure in large proportion of head and neck squamous cell carcinoma (HNSCC) patients requiring multimodal therapy involving chemotherapy in conjunction with surgery and/or radiotherapy. Molecular events conferring chemoresistance remain unclear. This project investigates a number of chemical, biological and physical strategies for targeting molecular vulnerabilities of chemoresistant cancer cells whilst sparing non-cancer cells. A large panel of chemical library consisting of synthetic and natural compounds will be screened using human cell culture models. We aim to identify the most potent multimodal anticancer therapy with the least toxicity to prevent or reverse chemoresistance in HNSCC patients.
Key References
Key References
1 Teh, M. T. et al. FOXM1 is a downstream target of Gli1 in basal cell carcinomas. Cancer Res. 62, 4773-4780 (2002).2 Gemenetzidis, E. et al. Induction of human epithelial stem/progenitor expansion by FOXM1. Cancer Res. 70, 9515-9526 (2010).3 Teh, M. T., Quinn, A. G. & Philpott, M. P. The Human forkhead transcription factor FOXM1B enhances DNA repair and suppresses UVB-induced apoptosis. Br. J. Dermatol. 152, 842-843 (2005).4 Gemenetzidis, E. et al. FOXM1 upregulation is an early event in human squamous cell carcinoma and it is enhanced by nicotine during malignant transformation. PLoS ONE 4, e4849 (2009).5 Teh, M. T., Gemenetzidis, E., Chaplin, T., Young, B. D. & Philpott, M. P. Upregulation of FOXM1 induces genomic instability in human epidermal keratinocytes. Mol. Cancer 9, 45 (2010).6 Waseem, A., Ali, M., Odell, E. W., Fortune, F. & Teh, M. T. Downstream targets of FOXM1: CEP55 and HELLS are cancer progression markers of head and neck squamous cell carcinoma. Oral Oncol. 46, 536-542 (2010).7 Teh, M. T. in Stem Cells and Cancer Stem Cells,Volume 3 Vol. 3 Stem Cells and Cancer Stem Cells (ed M. A. Hayat) Ch. Chapter 14, 149-154 (Springer Netherlands, 2012).8 Teh, M. T. Cells brainwashed by FOXM1: do they have potential as biomarkers of cancer? Biomark Med 6, 499-501 (2012).9 Teh, M. T. FOXM1 coming of age: time for translation into clinical benefits? Front Oncol 2, 146 (2012).10 Teh, M. T. et al. FOXM1 induces a global methylation signature that mimics the cancer epigenome in head and neck squamous cell carcinoma. PLoS ONE 7, e34329 (2012).11 Hwang, S. et al. Identification of FOXM1-induced epigenetic markers for head and neck squamous cell carcinomas. Cancer 119, 4249-4258 (2013).12 Shen, V. 2010 Molecule of the Year. Biotechniques, http://archive.is/jldm (2011).13 Teh, M. T. et al. Exploiting FOXM1-orchestrated molecular network for early squamous cell carcinoma diagnosis and prognosis. Int. J. Cancer 132, 2095-2106 (2013).14 Ma, H. et al. Independent evaluation of a FOXM1-based quantitative malignancy diagnostic system (qMIDS) on head and neck squamous cell carcinomas. Oncotarget 7, 54555-54563 (2016).15 Qadir, F. et al. Transcriptome reprogramming by cancer exosomes: identification of novel molecular targets in matrix and immune modulation. Mol. Cancer 17, 97 (2018).16 Qadir F. et al., Clinical correlation of opposing molecular signatures in head and neck squamous cell carcinoma. BMC Cancer 19, 830 (2019).17 Roh V. et al., The transcription factor FOXM1 regulates the balance between proliferation and aberrant differentiation in head and neck squamous cell carcinoma. J Pathol 250, 107-119 (2020).18 Aldehlawi H. et al., Serum lipids, retinoic acid and phenol red differentially regulate expression of keratins K1, K10 and K2 in cultured keratinocytes. Sci Rep 10, 4829 (2020).19 Liang Y. Y. et al., RASSF1A inhibits PDGFB-driven malignant phenotypes of nasopharyngeal carcinoma cells in a YAP1-dependent manner. Cell Death Dis 11, 855 (2020).20 García-González et al., Identification of slit3 as a locus affecting nicotine preference in zebrafish and human smoking behaviour. Elife 9:e51295 (2020)21 Teh, M. T. et al. Molecular Signatures of Tumour and Its Microenvironment for Precise Quantitative Diagnosis of OSCC: An International Multi-Cohort Diagnostic Validation Study. Cancers 2022, 14, 1389.22 Usman, S.; Waseem, N.H.; Nguyen, T.K.N.; Mohsin, S.; Jamal, A.; Teh, M.-T.; Waseem, A. Vimentin Is at the Heart of Epithelial Mesenchymal Transition (EMT) Mediated Metastasis. Cancers 2021, 13, 4985. 23 Usman, S.; Aldehlawi, H.; Nguyen, T.K.N.; Teh, M.-T.; Waseem, A. Impact of N-Terminal Tags on De Novo Vimentin Intermediate Filament Assembly. Int. J. Mol. Sci. 2022, 23, 6349. 24 Usman, S.; Jamal, A.; Bushaala, A.; Waseem, N.H.; Al-Dehlawi, H.; Yeudall, W.A.; Teh, M.-T.; Tummala, H.; Waseem, A. Transcriptome Analysis Reveals Vimentin-Induced Disruption of Cell–Cell Associations Augments Breast Cancer Cell Migration. Cells 2022, 11, 4035. 25 Sapkota, D., Sharma, S., Søland, T. M., Braz-Silva, P. H., & Teh, M.-T. (2022). Expression profile of SARS-CoV-2 cellular entry proteins in normal oral mucosa and oral squamous cell carcinoma. Clinical and Experimental Dental Research, 8, 117–122. 26 Perussolo, J., Teh, MT., Gkranias, N. et al. Efficacy of three antimicrobial mouthwashes in reducing SARS-CoV-2 viral load in the saliva of hospitalized patients: a randomized controlled pilot study. Sci Rep 13, 12647 (2023). 27 Khera, N; et al Teh, M.T. Identification of multidrug chemoresistant genes in head and neck squamous cell carcinoma cells. Mol. Cancer 22, 146 (2023).
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