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

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.

Citation

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., & Leigh, I. M. (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), 1159–1166. https://doi.org/10.1016/j.jaad.2023.08.012

DOI

10.1016/j.jaad.2023.08.012

URI

https://hdl.handle.net/20.500.14709/483

Usage rights

CC BY-NC-ND 4.0

License

https://creativecommons.org/licenses/by-nc-nd/4.0/