‘Cytology-on-a-chip’ based sensors for monitoring of potentially malignant oral lesions

Timothy J. Abram, Pierre N. Floriano, Nicolaos Christodoulides, Robert James, A. Ross Kerr, Martin H. Thornhill, Spencer W. Redding, Nadarajah Vigneswaran, Paul M. Speight, Julie Vick, Craig Murdoch, Christine Freeman, Anne M. Hegarty, Katy D'Apice, Joan A. Phelan, Patricia M. Corby, Ismael Khouly, Jerry Bouquot, Nagi M. Demian, Y. Etan WeinstockStephanie Rowan, Chih Ko Yeh, H. Stan McGuff, Frank R. Miller, Surabhi Gaur, Kailash Karthikeyan, Leander Taylor, Cathy Le, Michael Nguyen, Humberto Talavera, Rameez Raja, Jorge Wong, John T. McDevitt

Research output: Contribution to journalArticle

Abstract

Despite significant advances in surgical procedures and treatment, long-term prognosis for patients with oral cancer remains poor, with survival rates among the lowest of major cancers. Better methods are desperately needed to identify potential malignancies early when treatments are more effective. Objective To develop robust classification models from cytology-on-a-chip measurements that mirror diagnostic performance of gold standard approach involving tissue biopsy. Materials and methods Measurements were recorded from 714 prospectively recruited patients with suspicious lesions across 6 diagnostic categories (each confirmed by tissue biopsy -histopathology) using a powerful new ‘cytology-on-a-chip’ approach capable of executing high content analysis at a single cell level. Over 200 cellular features related to biomarker expression, nuclear parameters and cellular morphology were recorded per cell. By cataloging an average of 2000 cells per patient, these efforts resulted in nearly 13 million indexed objects. Results Binary “low-risk”/“high-risk” models yielded AUC values of 0.88 and 0.84 for training and validation models, respectively, with an accompanying difference in sensitivity + specificity of 6.2%. In terms of accuracy, this model accurately predicted the correct diagnosis approximately 70% of the time, compared to the 69% initial agreement rate of the pool of expert pathologists. Key parameters identified in these models included cell circularity, Ki67 and EGFR expression, nuclear-cytoplasmic ratio, nuclear area, and cell area. Conclusions This chip-based approach yields objective data that can be leveraged for diagnosis and management of patients with PMOL as well as uncovering new molecular-level insights behind cytological differences across the OED spectrum.

Original languageEnglish (US)
Pages (from-to)103-111
Number of pages9
JournalOral Oncology
Volume60
DOIs
StatePublished - Sep 1 2016

Keywords

  • Cytology
  • High content analysis
  • LASSO
  • Machine learning
  • Microfluidic
  • Oral cancer
  • Oral epithelial dysplasia
  • Random forest

ASJC Scopus subject areas

  • Oral Surgery
  • Oncology
  • Cancer Research

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    Abram, T. J., Floriano, P. N., Christodoulides, N., James, R., Kerr, A. R., Thornhill, M. H., Redding, S. W., Vigneswaran, N., Speight, P. M., Vick, J., Murdoch, C., Freeman, C., Hegarty, A. M., D'Apice, K., Phelan, J. A., Corby, P. M., Khouly, I., Bouquot, J., Demian, N. M., ... McDevitt, J. T. (2016). ‘Cytology-on-a-chip’ based sensors for monitoring of potentially malignant oral lesions. Oral Oncology, 60, 103-111. https://doi.org/10.1016/j.oraloncology.2016.07.002