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Molecular Diagnostics

Predicting the clinical outcome of oral potentially malignant disorders using transcriptomic-based molecular pathology

British Journal of Cancer volume 125, pages 413–421 (2021)Cite this article

Subjects

Abstract

Background

This study was undertaken to develop and validate a gene expression signature that characterises oral potentially malignant disorders (OPMD) with a high risk of undergoing malignant transformation.

Methods

Patients with oral epithelial dysplasia at one hospital were selected as the ‘training set’ (n = 56) whilst those at another hospital were selected for the ‘test set’ (n = 66). RNA was extracted from formalin-fixed paraffin-embedded (FFPE) diagnostic biopsies and analysed using the NanoString nCounter platform. A targeted panel of 42 genes selected on their association with oral carcinogenesis was used to develop a prognostic gene signature. Following data normalisation, uni- and multivariable analysis, as well as prognostic modelling, were employed to develop and validate the gene signature.

Results

A prognostic classifier composed of 11 genes was developed using the training set. The multivariable prognostic model was used to predict patient risk scores in the test set. The prognostic gene signature was an independent predictor of malignant transformation when assessed in the test set, with the high-risk group showing worse prognosis [Hazard ratio = 12.65, p = 0.0003].

Conclusions

This study demonstrates proof of principle that RNA extracted from FFPE diagnostic biopsies of OPMD, when analysed on the NanoString nCounter platform, can be used to generate a molecular classifier that stratifies the risk of malignant transformation with promising clinical utility.

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Fig. 1: Bar plot showing the predicted risk scores of the samples in the test set.
Fig. 2: Kaplan–Meier time to event analysis using Cox proportional hazards model comparing malignant transformation in the test set samples divided into low- or high-risk groups.

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References

  1. El-Naggar, A. K., Chan, J. K. C., Grandis, J. R., Takata, T., Slootweg, P. J., editors WHO Classification of Head and Neck Tumours (International Agency for Research on Cancer, 2017).

  2. Barnes, L., Eveson, J. W., Reichart, P., Sidransky, D., editors Pathology and Genetics of Head and Neck Tumours (World Health Organization, IARC, 2005).

  3. Moore, S., Johnson, N., Pierce, A. & Wilson, D. The epidemiology of lip cancer: a review of global incidence and aetiology. Oral Dis. 5, 185–195 (1999).

    Article  CAS  PubMed  Google Scholar 

  4. Moore, S. R., Johnson, N. W., Pierce, A. M. & Wilson, D. F. The epidemiology of mouth cancer: a review of global incidence. Oral Dis. 6, 65–74 (2000).

    Article  CAS  PubMed  Google Scholar 

  5. Warnakulasuriya, S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 45, 309–316 (2009).

    Article  PubMed  Google Scholar 

  6. Goodson, M. L. & Thomson, P. J. Management of oral carcinoma: benefits of early precancerous intervention. Br. J. Oral Maxillofac. Surg. 49, 88–91 (2011).

    Article  CAS  PubMed  Google Scholar 

  7. van der Waal, I. Potentially malignant disorders of the oral and oropharyngeal mucosa; terminology, classification and present concepts of management. Oral Oncol. 45, 317–323 (2009).

    Article  PubMed  Google Scholar 

  8. Warnakulasuriya, S., Johnson, N. W. & van der Waal, I. Nomenclature and classification of potentially malignant disorders of the oral mucosa. J. Oral Pathol. Med. 36, 575–580 (2007).

    Article  CAS  PubMed  Google Scholar 

  9. Warnakulasuriya, S. & Ariyawardana, A. Malignant transformation of oral leukoplakia: a systematic review of observational studies. J. Oral Pathol. Med. 45, 155–166 (2016).

    Article  CAS  PubMed  Google Scholar 

  10. Shariff, J. A. & Zavras, A. I. Malignant transformation rate in patients presenting oral epithelial dysplasia: systematic review and meta-analysis. J. Oral Dis. 2015, 1–10 (2015).

    Article  Google Scholar 

  11. Mehanna, H. M., Rattay, T., Smith, J. & McConkey, C. C. Treatment and follow-up of oral dysplasia—a systematic review and meta-analysis. Head Neck 31, 1600–1609 (2009).

    Article  PubMed  Google Scholar 

  12. Thomson, P. J., Goodson, M. L. & Smith, D. R. Profiling cancer risk in oral potentially malignant disorders—a patient cohort study. J. Oral Pathol. Med. 46, 888–895 (2017).

    CAS  PubMed  Google Scholar 

  13. Napier, S. S. & Speight, P. M. Natural history of potentially malignant oral lesions and conditions: an overview of the literature. J. Oral Pathol. Med. 37, 1–10 (2008).

    Article  PubMed  Google Scholar 

  14. Field, E. A., McCarthy, C. E., Ho, M. W., Rajlawat, B. P., Holt, D., Rogers, S. N. et al. The management of oral epithelial dysplasia: the Liverpool algorithm. Oral Oncol. 51, 883–887 (2015).

    Article  CAS  PubMed  Google Scholar 

  15. Villa, A. & Woo, S. B. Leukoplakia—a diagnostic and management algorithm. J. Oral Maxillofac. Surg. 75, 723–734 (2017).

    Article  PubMed  Google Scholar 

  16. Awadallah, M., Idle, M., Patel, K. & Kademani, D. Management update of potentially premalignant oral epithelial lesions. Oral Surg. Oral Med. Oral. Pathol. Oral Radiol. 125, 628–636 (2018).

    Article  PubMed  Google Scholar 

  17. Reibel, J. Prognosis of oral pre-malignant lesions: significance of clinical, histopathological, and molecular biological characteristics. Crit. Rev. Oral Biol. Med. 14, 47–62 (2003).

    Article  PubMed  Google Scholar 

  18. Pitiyage, G., Tilakaratne, W. M., Tavassoli, M. & Warnakulasuriya, S. Molecular markers in oral epithelial dysplasia: review. J. Oral Pathol. Med. 38, 737–752 (2009).

    Article  CAS  PubMed  Google Scholar 

  19. Nankivell, P. & Mehanna, H. Oral dysplasia: biomarkers, treatment, and follow-up. Curr. Oncol. Rep. 13, 145–152 (2011).

    Article  PubMed  Google Scholar 

  20. Smith, J., Rattay, T., McConkey, C., Helliwell, T. & Mehanna, H. Biomarkers in dysplasia of the oral cavity: a systematic review. Oral Oncol. 45, 647–653 (2009).

    Article  CAS  PubMed  Google Scholar 

  21. Lingen, M. W., Pinto, A., Mendes, R. A., Franchini, R., Czerninski, R., Tilakaratne, W. M. et al. Genetics/epigenetics of oral premalignancy: current status and future research. Oral Dis. 17, 7–22 (2011).

    Article  PubMed  Google Scholar 

  22. Nikitakis, N. G., Pentenero, M., Georgaki, M., Poh, C. F., Peterson, D. E., Edwards, P. et al. Molecular markers associated with development and progression of potentially premalignant oral epithelial lesions: Current knowledge and future implications. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 125, 650–669 (2018).

    Article  PubMed  Google Scholar 

  23. Speight, P. M., Khurram, S. A. & Kujan, O. Oral potentially malignant disorders: risk of progression to malignancy. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 125, 612–627 (2018).

    Article  PubMed  Google Scholar 

  24. De Cecco, L., Nicolau, M., Giannoccaro, M., Daidone, M. G., Bossi, P., Locati, L. et al. Head and neck cancer subtypes with biological and clinical relevance: meta-analysis of gene-expression data. Oncotarget 6, 9627–9642 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  25. Tonella, L., Giannoccaro, M., Alfieri, S., Canevari, S. & De Cecco, L. Gene expression signatures for head and neck cancer patient stratification: are results ready for clinical application? Curr. Treat. Options Oncol. 18, 32 (2017).

    Article  PubMed  Google Scholar 

  26. Saintigny, P., Zhang, L., Fan, Y. H., El-Naggar, A. K., Papadimitrakopoulou, V. A., Feng, L. et al. Gene expression profiling predicts the development of oral cancer. Cancer Prev. Res. (Philos.) 4, 218–229 (2011).

    Article  CAS  Google Scholar 

  27. Geiss, G. K., Bumgarner, R. E., Birditt, B., Dahl, T., Dowidar, N., Dunaway, D. L. et al. Direct multiplexed measurement of gene expression with color-coded probe pairs. Nat. Biotechnol. 26, 317–325 (2008).

    Article  CAS  PubMed  Google Scholar 

  28. Reis, P. P., Waldron, L., Goswami, R. S., Xu, W., Xuan, Y., Perez-Ordonez, B. et al. mRNA transcript quantification in archival samples using multiplexed, color-coded probes. BMC Biotechnol. 11, 46 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Balko, J. M., Cook, R. S., Vaught, D. B., Kuba, M. G., Miller, T. W., Bhola, N. E. et al. Profiling of residual breast cancers after neoadjuvant chemotherapy identifies DUSP4 deficiency as a mechanism of drug resistance. Nat. Med. 18, 1052–1059 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Veldman-Jones, M. H., Brant, R., Rooney, C., Geh, C., Emery, H., Harbron, C. G. et al. Evaluating robustness and sensitivity of the NanoString technologies nCounter platform to enable multiplexed gene expression analysis of clinical samples. Cancer Res. 75, 2587–2593 (2015).

    Article  CAS  PubMed  Google Scholar 

  31. Veldman-Jones, M. H., Lai, Z., Wappett, M., Harbron, C. G., Barrett, J. C., Harrington, E. A. et al. Reproducible, quantitative, and flexible molecular subtyping of clinical DLBCL samples using the NanoString nCounter system. Clin. Cancer Res. 21, 2367–2378 (2015).

    Article  CAS  PubMed  Google Scholar 

  32. Speight, P. M., Abram, T. J., Floriano, P. N., James, R., Vick, J., Thornhill, M. H. et al. Interobserver agreement in dysplasia grading: toward an enhanced gold standard for clinical pathology trials. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 120, 474–482 e2 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  33. Kujan, O., Oliver, R. J., Khattab, A., Roberts, S. A., Thakker, N. & Sloan, P. Evaluation of a new binary system of grading oral epithelial dysplasia for prediction of malignant transformation. Oral Oncol. 42, 987–993 (2006).

    Article  PubMed  Google Scholar 

  34. NanoString. nCounter XT Assay User Manual (NanoString Technologies Inc., 2016).

  35. Sathasivam, H. P., Casement, J., Bates, T., Sloan, P., Thomson, P., Robinson, M., et al. Gene expression changes associated with malignant transformation of oral potentially malignant disorders. J. Oral Pathol. Med. https://doi.org/10.1111/jop.13090 (2020).

  36. Lohavanichbutr, P., Méndez, E., Holsinger, F. C., Rue, T. C., Zhang, Y., Houck, J. et al. A 13-gene signature prognostic of HPV-negative OSCC: discovery and external validation. Clin. Cancer Res. 19, 1197 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Lallemant, B., Evrard, A., Combescure, C., Chapuis, H., Chambon, G., Raynal, C. et al. Reference gene selection for head and neck squamous cell carcinoma gene expression studies. BMC Mol. Biol. 10, 78 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Taïhi, I., Nassif, A., Berbar, T., Isaac, J., Berdal, A., Gogly, B. et al. Validation of housekeeping genes to study human gingival stem cells and their in vitro osteogenic differentiation using real-time RT-qPCR. Stem Cells Int. 2016, 6261490 (2016).

    Article  PubMed  CAS  Google Scholar 

  39. Rentoft, M., Hultin, S., Coates, P. J., Laurell, G. & Nylander, K. Tubulin α-6 chain is a stably expressed reference gene in archival samples of normal oral tissue and oral squamous cell carcinoma. Exp. Ther. Med. 1, 419–423 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Haider, S., Yao, C. Q., Sabine, V. S., Grzadkowski, M., Stimper, V., Starmans, M. H. W. et al. Pathway-based subnetworks enable cross-disease biomarker discovery. Nat. Commun. 9, 4746 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Ye, H., Yu, T., Temam, S., Ziober, B. L., Wang, J., Schwartz, J. L. et al. Transcriptomic dissection of tongue squamous cell carcinoma. BMC Genomics 9, 69 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. van der Waal, I. Potentially malignant disorders of the oral and oropharyngeal mucosa; present concepts of management. Oral Oncol. 46, 423–425 (2010).

    Article  PubMed  Google Scholar 

  43. Dost, F., Le Cao, K., Ford, P. J., Ades, C. & Farah, C. S. Malignant transformation of oral epithelial dysplasia: a real-world evaluation of histopathologic grading. Oral Surg. Oral Med Oral Pathol. Oral Radiol. 117, 343–352 (2014).

    Article  CAS  PubMed  Google Scholar 

  44. Hald, J., Overgaard, J. & Grau, C. Evaluation of objective measures of smoking status–a prospective clinical study in a group of head and neck cancer patients treated with radiotherapy. Acta Oncol. 42, 154–159 (2003).

    Article  PubMed  Google Scholar 

  45. von Ahlfen, S., Missel, A., Bendrat, K. & Schlumpberger, M. Determinants of RNA quality from FFPE samples. PLoS ONE 2, e1261 (2007).

    Article  CAS  Google Scholar 

  46. Eikrem, O., Beisland, C., Hjelle, K., Flatberg, A., Scherer, A., Landolt, L. et al. Transcriptome sequencing (RNAseq) enables utilization of formalin-fixed, paraffin-embedded biopsies with clear cell renal cell carcinoma for exploration of disease biology and biomarker development. PLoS ONE 11, e0149743 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Mittempergher, L., de Ronde, J. J., Nieuwland, M., Kerkhoven, R. M., Simon, I., Rutgers, E. J. et al. Gene expression profiles from formalin fixed paraffin embedded breast cancer tissue are largely comparable to fresh frozen matched tissue. PLoS ONE 6, e17163 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Wimmer, I., Troscher, A. R., Brunner, F., Rubino, S. J., Bien, C. G., Weiner, H. L. et al. Systematic evaluation of RNA quality, microarray data reliability and pathway analysis in fresh, fresh frozen and formalin-fixed paraffin-embedded tissue samples. Sci. Rep. 8, 6351 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Scott, D. W., Chan, F. C., Hong, F., Rogic, S., Tan, K. L., Meissner, B. et al. Gene expression-based model using formalin-fixed paraffin-embedded biopsies predicts overall survival in advanced-stage classical Hodgkin lymphoma. J. Clin. Oncol. 31, 692–700 (2013).

    Article  PubMed  Google Scholar 

  50. Saba, N. F., Wilson, M., Doho, G., DaSilva, J., Benjamin Isett, R., Newman, S. et al. Mutation and transcriptional profiling of formalin-fixed paraffin embedded specimens as companion methods to immunohistochemistry for determining therapeutic targets in oropharyngeal squamous cell carcinoma (OPSCC): a pilot of proof of principle. Head Neck Pathol. 9, 223–235 (2015).

    Article  PubMed  Google Scholar 

  51. Scaltriti, M., Eichhorn, P. J., Cortes, J., Prudkin, L., Aura, C., Jimenez, J. et al. Cyclin E amplification/overexpression is a mechanism of trastuzumab resistance in HER2+ breast cancer patients. Proc. Natl Acad. Sci. USA 108, 3761–3766 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Cancer Genome Atlas N. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 517, 576–582 (2015).

    Article  CAS  Google Scholar 

  53. Hatano, M., Roberts, C. W., Minden, M., Crist, W. M. & Korsmeyer, S. J. Deregulation of a homeobox gene, HOX11, by the t(10;14) in T cell leukemia. Science 253, 79–82 (1991).

    Article  CAS  PubMed  Google Scholar 

  54. Yap, L. F., Lee, D., Khairuddin, A., Pairan, M. F., Puspita, B., Siar, C. H. et al. The opposing roles of NOTCH signalling in head and neck cancer: a mini review. Oral Dis. 21, 850–857 (2015).

    Article  CAS  PubMed  Google Scholar 

  55. Ranganathan, P., Weaver, K. L. & Capobianco, A. J. Notch signalling in solid tumours: a little bit of everything but not all the time. Nat. Rev. Cancer 11, 338–351 (2011).

    Article  CAS  PubMed  Google Scholar 

  56. Agrawal, N., Frederick, M. J., Pickering, C. R., Bettegowda, C., Chang, K., Li, R. J. et al. Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science 333, 1154–1157 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Alevizos, I., Mahadevappa, M., Zhang, X., Ohyama, H., Kohno, Y., Posner, M. et al. Oral cancer in vivo gene expression profiling assisted by laser capture microdissection and microarray analysis. Oncogene 20, 6196–6204 (2001).

    Article  CAS  PubMed  Google Scholar 

  58. Macabeo-Ong, M., Shiboski, C. H., Silverman, S., Ginzinger, D. G., Dekker, N., Wong, D. T. et al. Quantitative analysis of cathepsin L mRNA and protein expression during oral cancer progression. Oral Oncol. 39, 638–647 (2003).

    Article  CAS  PubMed  Google Scholar 

  59. Kang, C.-J., Chen, Y.-J., Liao, C.-T., Wang, H.-M., Chang, J. T., Lin, C.-Y. et al. Transcriptome profiling and network pathway analysis of genes associated with invasive phenotype in oral cancer. Cancer Lett. 284, 131–140 (2009).

    Article  CAS  PubMed  Google Scholar 

  60. Mallery, S. R., Zwick, J. C., Pei, P., Tong, M., Larsen, P. E., Shumway, B. S. et al. Topical application of a bioadhesive black raspberry gel modulates gene expression and reduces cyclooxygenase 2 protein in human premalignant oral lesions. Cancer Res. 68, 4945 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Kuriakose, M. A., Chen, W. T., He, Z. M., Sikora, A. G., Zhang, P., Zhang, Z. Y. et al. Selection and validation of differentially expressed genes in head and neck cancer. Cell. Mol. Life Sci. 61, 1372–1383 (2004).

    Article  CAS  PubMed  Google Scholar 

  62. Leemans, C. R., Braakhuis, B. J. & Brakenhoff, R. H. The molecular biology of head and neck cancer. Nat. Rev. Cancer 11, 9–22 (2011).

    Article  CAS  PubMed  Google Scholar 

  63. Brennan, J. A., Boyle, J. O., Koch, W. M., Goodman, S. N., Hruban, R. H., Eby, Y. J. et al. Association between cigarette smoking and mutation of the p53 gene in squamous-cell carcinoma of the head and neck. N. Engl. J. Med. 332, 712–717 (1995).

    Article  CAS  PubMed  Google Scholar 

  64. Apostolou, P. & Papasotiriou, I. Current perspectives on CHEK2 mutations in breast cancer. Breast Cancer (Dove Med. Press) 9, 331–335 (2017).

    CAS  Google Scholar 

  65. Cybulski, C., Górski, B., Huzarski, T., Masojć, B., Mierzejewski, M., Debniak, T. et al. CHEK2 is a multiorgan cancer susceptibility gene. Am. J. Hum. Genet. 75, 1131–1135 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Cybulski, C., Huzarski, T., Górski, B., Masojć, B., Mierzejewski, M., Debniak, T. et al. A novel founder CHEK2 mutation is associated with increased prostate cancer risk. Cancer Res. 64, 2677–2679 (2004).

    Article  CAS  PubMed  Google Scholar 

  67. Chen, Y.-L., Tsai, W.-H., Ko, Y.-C., Lai, T.-Y., Cheng, A.-J., Shiah, S.-G. et al. Discoidin domain receptor-1 (DDR1) is involved in angiolymphatic invasion in oral cancer. Cancers (Basel) 12, 841 (2020).

    Article  CAS  Google Scholar 

  68. Wang, W. W., Wang, Y. B., Wang, D. Q., Lin, Z. & Sun, R. J. Integrin beta-8 (ITGB8) silencing reverses gefitinib resistance of human hepatic cancer HepG2/G cell line. Int. J. Clin. Exp. Med. 8, 3063–3071 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Cui, Y., Wu, F., Tian, D., Wang, T., Lu, T., Huang, X. et al. miR-199a-3p enhances cisplatin sensitivity of ovarian cancer cells by targeting ITGB8. Oncol. Rep. 39, 1649–1657 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Mertens-Walker, I., Fernandini, B. C., Maharaj, M. S., Rockstroh, A., Nelson, C. C., Herington, A. C. et al. The tumour-promoting receptor tyrosine kinase, EphB4, regulates expression of integrin-beta8 in prostate cancer cells. BMC Cancer 15, 164 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Lenouvel, D., González-Moles, M. Á., Talbaoui, A., Ramos-García, P., González-Ruiz, L., Ruiz-Ávila, I. et al. An update of knowledge on PD-L1 in head and neck cancers: physiologic, prognostic and therapeutic perspectives. Oral Dis. 26, 511–526 (2020).

    Article  PubMed  Google Scholar 

  72. Dave, K., Ali, A. & Magalhaes, M. Increased expression of PD-1 and PD-L1 in oral lesions progressing to oral squamous cell carcinoma: a pilot study. Sci. Rep. 10, 9705 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Saintigny, P., El-Naggar, A. K., Papadimitrakopoulou, V., Ren, H., Fan, Y. H., Feng, L. et al. DeltaNp63 overexpression, alone and in combination with other biomarkers, predicts the development of oral cancer in patients with leukoplakia. Clin. Cancer Res. 15, 6284–6291 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Matsubara, R., Kawano, S., Kiyosue, T., Goto, Y., Hirano, M., Jinno, T. et al. Increased DeltaNp63 expression is predictive of malignant transformation in oral epithelial dysplasia and poor prognosis in oral squamous cell carcinoma. Int. J. Oncol. 39, 1391–1399 (2011).

    CAS  PubMed  Google Scholar 

  75. Chen, Y. K., Hsue, S. S. & Lin, L. M. Expression of p63 protein and mRNA in oral epithelial dysplasia. J. Oral Pathol. Med. 34, 232–239 (2005).

    Article  CAS  PubMed  Google Scholar 

  76. Chibon, F. Cancer gene expression signatures—the rise and fall? Eur. J. Cancer 49, 2000–2009 (2013).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We would like to acknowledge Ms. Anastasia Resteu from the Newcastle NanoString Unit, Newcastle University, for assisting with the NanoString assay.

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Author notes

  1. These authors contributed equally: Hans Prakash Sathasivam, Ralf Kist, Syed Haider, Max Robinson

Authors and Affiliations

  1. School of Dental Sciences, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK

    Hans Prakash Sathasivam, Ralf Kist, Philip Sloan & Max Robinson

  2. Cancer Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, Setia Alam, Malaysia

    Hans Prakash Sathasivam

  3. Newcastle University Biosciences Institute, Newcastle University Centre for Cancer, Newcastle upon Tyne, UK

    Ralf Kist

  4. Department of Cellular Pathology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK

    Philip Sloan & Max Robinson

  5. Oral and Maxillofacial Surgery, Faculty of Dentistry, The University of Hong Kong, Hong Kong, Hong Kong SAR

    Peter Thomson

  6. Oral and Maxillofacial Surgery, Sunderland Royal Hospital, Sunderland, UK

    Michael Nugent

  7. The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK

    John Alexander & Syed Haider

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Contributions

H.P.S. conceived and designed the study, performed experiments, analysed data, carried out statistical analysis and wrote major parts of the manuscript. R.K. participated in study design, provided expert advice, performed experiments, interpreted results and edited the manuscript. P.S. participated in study design, provided expert advice, performed dysplasia grading, contributed to retrieval of tissue, interpreted results and edited the manuscript. P.T. and M.N. contributed to case selection, retrieval of follow-up data, quality assurance of data, interpreted results and edited the manuscript. J.A. and S.H. contributed to study design, analysed data, carried out statistical analysis, quality assurance of results, interpreted results and wrote major parts of the manuscript. M.R. conceived and designed the study, provided expert advice, performed dysplasia grading, contributed to retrieval of tissue, analysed data, interpreted results and wrote major parts of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Max Robinson.

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Ethics approval and consent to participate

The study was performed with approval from a Health Research Authority (UK) Research Ethics Committee (North East—Tyne and Wear South Research Ethics Committee; NRES Committee North East—Sunderland 11/NE/0118) and complies with UK legislation and guidelines. Patients were not recruited to the study and therefore individual patient consent was not sought. Link-anonymised patient tissue samples, surplus to diagnostic requirements, were analysed in accordance with the terms of the ethical approval. The study was performed in accordance with the Declaration of Helsinki.

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Not applicable.

Data availability

The datasets used and/or analysed during the current study are available at https://doi.org/10.5281/zenodo.4643470.

Competing interests

The authors declare no competing interests.

Funding information

H.P. Sathasivam was supported by scholarship from Ministry of Health Malaysia. S.H. is supported by Breast Cancer Now as part of Programme Funding to The Breast Cancer Now Toby Robins Research Centre.

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Sathasivam, H.P., Kist, R., Sloan, P. et al. Predicting the clinical outcome of oral potentially malignant disorders using transcriptomic-based molecular pathology. Br J Cancer 125, 413–421 (2021). https://doi.org/10.1038/s41416-021-01411-z

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