Transcriptomic analysis of cutaneous squamous cell carcinoma reveals a multigene prognostic signature associated with metastasis

Wang, J. et al. (2023) Transcriptomic analysis of cutaneous squamous cell carcinoma reveals a multigene prognostic signature associated with metastasis. Journal of the American Academy of Dermatology, 89(6), pp. 1159-1166. (doi: 10.1016/j.jaad.2023.08.012) (PMID:37586461)

Abstract

Background Metastasis of cutaneous squamous cell carcinoma (cSCC) is uncommon. Current staging methods are reported to have sub-optimal performances in metastasis prediction. Accurate identification of patients with tumors at high risk of metastasis would have a significant impact on management. Objective To develop a robust and validated gene expression profile signature for predicting primary cSCC metastatic risk using an unbiased whole transcriptome discovery-driven approach. Methods Archival formalin-fixed paraffin-embedded primary cSCC with perilesional normal tissue from 237 immunocompetent patients (151 nonmetastasizing and 86 metastasizing) were collected retrospectively from four centers. TempO-seq was used to probe the whole transcriptome and machine learning algorithms were applied to derive predictive signatures, with a 3:1 split for training and testing datasets. Results A 20-gene prognostic model was developed and validated, with an accuracy of 86.0%, sensitivity of 85.7%, specificity of 86.1%, and positive predictive value of 78.3% in the testing set, providing more stable, accurate prediction than pathological staging systems. A linear predictor was also developed, significantly correlating with metastatic risk. Limitations This was a retrospective 4-center study and larger prospective multicenter studies are now required. Conclusion The 20-gene signature prediction is accurate, with the potential to be incorporated into clinical workflows for cSCC.

• Item Type: Articles
• Additional Information: J.W., E.B., F.B.C., and C.A.A. acknowledge support from Cancer Research UK City of London Major Centre core funding support to Barts Cancer Institute (C16420/ A18066). J.W., C.H., E.B., and I.M.L. also acknowledge funding support from The Barts Charity Strategic Award of Barts Centre and Squamous Cancer (MGU0603). J.W. also acknowledges support from Cancer Research UK (C355/ A26819) and FC AECC and AIRC under the Accelerator Award Program, and support from the Academy of Medical Sciences Springboard Award (SBF003/1025). C.N., C.S., M.T.T. and G.J.I. acknowledge support from Cancer Research UK (A29802) and M.T.T. is funded by a Cancer Research UK-Funded TRACC PhD studentship. C.L. is funded by the MRC Clinical Academic Research Partnerships (CARP).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Moyes, Colin and Schoenherr, Dr Christina and Nourse, Dr Craig and Inman, Professor Gareth and Treanor-Taylor, Ms Mairi
• Authors: Wang, J., Harwood, C. A., Bailey, E., Bewicke-Copley, F., Anene, C. A., Thomson, J., Qamar, M. J., Laban, R., Nourse, C., Schoenherr, C., Treanor-Taylor, M., Healy, E., Lai, C., Craig, P., Moyes, C., Rickaby, W., Martin, J., Proby, C., Inman, G. J., and Leigh, I. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Journal of the American Academy of Dermatology
• Publisher: Elsevier
• ISSN: 0190-9622
• Copyright Holders: Copyright: © 2023 by the American Academy of Dermatology, Inc.
• First Published: First published in Journal of the American Academy of Dermatology 89(6): 1159-1166
• Publisher Policy: Reproduced under a Creative Commons licence