Wang, Jun and Harwood, Catherine A. and Bailey, Emma and Bewicke-Copley, Findlay and Anene, Chinedu Anthony and Thomson, Jason and Qamar, Mah Jabeen and Laban, Rhiannon and Nourse, Craig and Schoenherr, Christina and Treanor-Taylor, Mairi and Healy, Eugene and Lai, Chester and Craig, Paul and Moyes, Colin and Rickaby, William and Martin, Joanne and Proby, Charlotte and Inman, Gareth J. and Leigh, Irene 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). pp. 1159-1166. ISSN 0190-9622

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.

People
Wang, Jun
Author

Maldonado, Horacio and Dreger, Marcel and Bedgood, Lara D. and Kyriakou, Theano and Wolanska, Katarzyna I. and Rigby, Megan E. and Marotta, Valeria E. and Webster, Justine M. and Wang, Jun and Rusilowicz-Jones, Emma V. and Marshall, John F. and Coulson, Judy M. and MacPherson, Iain R. and Hurlstone, Adam and Morgan, Mark R. (2024) A trafficking regulatory subnetwork governs α V β 6 integrin-HER2 cross-talk to control breast cancer invasion and drug resistance. Science Advances, 10 (49): eadk9944. ISSN 2375-2548

Wang, Jun and Harwood, Catherine A. and Bailey, Emma and Bewicke-Copley, Findlay and Anene, Chinedu Anthony and Thomson, Jason and Qamar, Mah Jabeen and Laban, Rhiannon and Nourse, Craig and Schoenherr, Christina and Treanor-Taylor, Mairi and Healy, Eugene and Lai, Chester and Craig, Paul and Moyes, Colin and Rickaby, William and Martin, Joanne and Proby, Charlotte and Inman, Gareth J. and Leigh, Irene 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). pp. 1159-1166. ISSN 0190-9622

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Harwood, Catherine A.
Author

Wang, Jun and Harwood, Catherine A. and Bailey, Emma and Bewicke-Copley, Findlay and Anene, Chinedu Anthony and Thomson, Jason and Qamar, Mah Jabeen and Laban, Rhiannon and Nourse, Craig and Schoenherr, Christina and Treanor-Taylor, Mairi and Healy, Eugene and Lai, Chester and Craig, Paul and Moyes, Colin and Rickaby, William and Martin, Joanne and Proby, Charlotte and Inman, Gareth J. and Leigh, Irene 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). pp. 1159-1166. ISSN 0190-9622

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Bailey, Emma
Author

Wang, Jun and Harwood, Catherine A. and Bailey, Emma and Bewicke-Copley, Findlay and Anene, Chinedu Anthony and Thomson, Jason and Qamar, Mah Jabeen and Laban, Rhiannon and Nourse, Craig and Schoenherr, Christina and Treanor-Taylor, Mairi and Healy, Eugene and Lai, Chester and Craig, Paul and Moyes, Colin and Rickaby, William and Martin, Joanne and Proby, Charlotte and Inman, Gareth J. and Leigh, Irene 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). pp. 1159-1166. ISSN 0190-9622

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Bewicke-Copley, Findlay
Author

Wang, Jun and Harwood, Catherine A. and Bailey, Emma and Bewicke-Copley, Findlay and Anene, Chinedu Anthony and Thomson, Jason and Qamar, Mah Jabeen and Laban, Rhiannon and Nourse, Craig and Schoenherr, Christina and Treanor-Taylor, Mairi and Healy, Eugene and Lai, Chester and Craig, Paul and Moyes, Colin and Rickaby, William and Martin, Joanne and Proby, Charlotte and Inman, Gareth J. and Leigh, Irene 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). pp. 1159-1166. ISSN 0190-9622

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Anene, Chinedu Anthony
Author

Wang, Jun and Harwood, Catherine A. and Bailey, Emma and Bewicke-Copley, Findlay and Anene, Chinedu Anthony and Thomson, Jason and Qamar, Mah Jabeen and Laban, Rhiannon and Nourse, Craig and Schoenherr, Christina and Treanor-Taylor, Mairi and Healy, Eugene and Lai, Chester and Craig, Paul and Moyes, Colin and Rickaby, William and Martin, Joanne and Proby, Charlotte and Inman, Gareth J. and Leigh, Irene 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). pp. 1159-1166. ISSN 0190-9622

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Thomson, Jason
Author

Wang, Jun and Harwood, Catherine A. and Bailey, Emma and Bewicke-Copley, Findlay and Anene, Chinedu Anthony and Thomson, Jason and Qamar, Mah Jabeen and Laban, Rhiannon and Nourse, Craig and Schoenherr, Christina and Treanor-Taylor, Mairi and Healy, Eugene and Lai, Chester and Craig, Paul and Moyes, Colin and Rickaby, William and Martin, Joanne and Proby, Charlotte and Inman, Gareth J. and Leigh, Irene 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). pp. 1159-1166. ISSN 0190-9622

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Qamar, Mah Jabeen
Author

Wang, Jun and Harwood, Catherine A. and Bailey, Emma and Bewicke-Copley, Findlay and Anene, Chinedu Anthony and Thomson, Jason and Qamar, Mah Jabeen and Laban, Rhiannon and Nourse, Craig and Schoenherr, Christina and Treanor-Taylor, Mairi and Healy, Eugene and Lai, Chester and Craig, Paul and Moyes, Colin and Rickaby, William and Martin, Joanne and Proby, Charlotte and Inman, Gareth J. and Leigh, Irene 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). pp. 1159-1166. ISSN 0190-9622

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Laban, Rhiannon
Author

Wang, Jun and Harwood, Catherine A. and Bailey, Emma and Bewicke-Copley, Findlay and Anene, Chinedu Anthony and Thomson, Jason and Qamar, Mah Jabeen and Laban, Rhiannon and Nourse, Craig and Schoenherr, Christina and Treanor-Taylor, Mairi and Healy, Eugene and Lai, Chester and Craig, Paul and Moyes, Colin and Rickaby, William and Martin, Joanne and Proby, Charlotte and Inman, Gareth J. and Leigh, Irene 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). pp. 1159-1166. ISSN 0190-9622

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Nourse, Craig
Author

Astuti, Yuliana and Raymant, Meirion and Quaranta, Valeria and Clarke, Kim and Abudula, Maidinaimu and Smith, Olivia and Bellomo, Gaia and Chandran-Gorner, Vatshala and Nourse, Craig and Halloran, Christopher and Ghaneh, Paula and Palmer, Daniel and Jones, Robert P and Campbell, Fiona and Pollard, Jeffrey W and Morton, Jennifer P. and Mielgo, Ainhoa and Schmid, Michael C (2024) Author correction: Efferocytosis reprograms the tumor microenvironment to promote pancreatic cancer liver metastasis. Nature Cancer, 5: 808. ISSN 2662-1347

Astuti, Yuliana and Raymant, Meirion and Quaranta, Valeria and Clarke, Kim and Abudula, Maidinaimu and Smith, Olivia and Bellomo, Gaia and Chandran-Gorner, Vatshala and Nourse, Craig and Halloran, Christopher and Ghaneh, Paula and Palmer, Daniel and Jones, Robert P. and Campbell, Fiona and Pollard, Jeffrey W. and Morton, Jennifer P. and Mielgo, Ainhoa and Schmid, Michael C. (2024) Efferocytosis reprograms the tumor microenvironment to promote pancreatic cancer liver metastasis. Nature Cancer, 5. pp. 774-790. ISSN 2662-1347

Wang, Jun and Harwood, Catherine A. and Bailey, Emma and Bewicke-Copley, Findlay and Anene, Chinedu Anthony and Thomson, Jason and Qamar, Mah Jabeen and Laban, Rhiannon and Nourse, Craig and Schoenherr, Christina and Treanor-Taylor, Mairi and Healy, Eugene and Lai, Chester and Craig, Paul and Moyes, Colin and Rickaby, William and Martin, Joanne and Proby, Charlotte and Inman, Gareth J. and Leigh, Irene 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). pp. 1159-1166. ISSN 0190-9622

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Schoenherr, Christina
Author

Singh, Shashi P. and Smyth, Danielle J. and Cunningham, Kyle T. and Mukundan, Ananya and Byeon, Chang-Hyeock and Hinck, Cynthia S. and White, Madeleine P.J. and Ciancia, Claire and Wąsowska, Natalia and Sanders, Anna and Jin, Regina and White, Ruby F. and Lilla, Sergio and Zanivan, Sara and Schoenherr, Christina and Inman, Gareth and van Dinther, Maarten and ten Dijke, Peter and Hinck, Andrew P. and Maizels, Rick M. (2025) The TGF-β mimic TGM4 achieves cell specificity through combinatorial surface co-receptor binding. EMBO Reports, 26 (1). pp. 218-244. ISSN 1469-221X

Strathearn, Lauren S. and Spender, Lindsay C. and Schoenherr, Christina and Mason, Susan and Edwards, Ruaridh and Blyth, Karen and Inman, Gareth (2024) C1orf106 (INAVA) is a SMAD3-dependent TGF-β target gene that promotes clonogenicity and correlates with poor prognosis in breast cancer. Cells, 13 (18): 1530. ISSN 2073-4409

Wang, Jun and Harwood, Catherine A. and Bailey, Emma and Bewicke-Copley, Findlay and Anene, Chinedu Anthony and Thomson, Jason and Qamar, Mah Jabeen and Laban, Rhiannon and Nourse, Craig and Schoenherr, Christina and Treanor-Taylor, Mairi and Healy, Eugene and Lai, Chester and Craig, Paul and Moyes, Colin and Rickaby, William and Martin, Joanne and Proby, Charlotte and Inman, Gareth J. and Leigh, Irene 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). pp. 1159-1166. ISSN 0190-9622

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Treanor-Taylor, Mairi
Author

Wang, Jun and Harwood, Catherine A. and Bailey, Emma and Bewicke-Copley, Findlay and Anene, Chinedu Anthony and Thomson, Jason and Qamar, Mah Jabeen and Laban, Rhiannon and Nourse, Craig and Schoenherr, Christina and Treanor-Taylor, Mairi and Healy, Eugene and Lai, Chester and Craig, Paul and Moyes, Colin and Rickaby, William and Martin, Joanne and Proby, Charlotte and Inman, Gareth J. and Leigh, Irene 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). pp. 1159-1166. ISSN 0190-9622

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Healy, Eugene
Author

Wang, Jun and Harwood, Catherine A. and Bailey, Emma and Bewicke-Copley, Findlay and Anene, Chinedu Anthony and Thomson, Jason and Qamar, Mah Jabeen and Laban, Rhiannon and Nourse, Craig and Schoenherr, Christina and Treanor-Taylor, Mairi and Healy, Eugene and Lai, Chester and Craig, Paul and Moyes, Colin and Rickaby, William and Martin, Joanne and Proby, Charlotte and Inman, Gareth J. and Leigh, Irene 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). pp. 1159-1166. ISSN 0190-9622

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Lai, Chester
Author

Wang, Jun and Harwood, Catherine A. and Bailey, Emma and Bewicke-Copley, Findlay and Anene, Chinedu Anthony and Thomson, Jason and Qamar, Mah Jabeen and Laban, Rhiannon and Nourse, Craig and Schoenherr, Christina and Treanor-Taylor, Mairi and Healy, Eugene and Lai, Chester and Craig, Paul and Moyes, Colin and Rickaby, William and Martin, Joanne and Proby, Charlotte and Inman, Gareth J. and Leigh, Irene 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). pp. 1159-1166. ISSN 0190-9622

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Craig, Paul
Author

Wang, Jun and Harwood, Catherine A. and Bailey, Emma and Bewicke-Copley, Findlay and Anene, Chinedu Anthony and Thomson, Jason and Qamar, Mah Jabeen and Laban, Rhiannon and Nourse, Craig and Schoenherr, Christina and Treanor-Taylor, Mairi and Healy, Eugene and Lai, Chester and Craig, Paul and Moyes, Colin and Rickaby, William and Martin, Joanne and Proby, Charlotte and Inman, Gareth J. and Leigh, Irene 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). pp. 1159-1166. ISSN 0190-9622

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Moyes, Colin
Author

Wang, Jun and Harwood, Catherine A. and Bailey, Emma and Bewicke-Copley, Findlay and Anene, Chinedu Anthony and Thomson, Jason and Qamar, Mah Jabeen and Laban, Rhiannon and Nourse, Craig and Schoenherr, Christina and Treanor-Taylor, Mairi and Healy, Eugene and Lai, Chester and Craig, Paul and Moyes, Colin and Rickaby, William and Martin, Joanne and Proby, Charlotte and Inman, Gareth J. and Leigh, Irene 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). pp. 1159-1166. ISSN 0190-9622

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Rickaby, William
Author

Wang, Jun and Harwood, Catherine A. and Bailey, Emma and Bewicke-Copley, Findlay and Anene, Chinedu Anthony and Thomson, Jason and Qamar, Mah Jabeen and Laban, Rhiannon and Nourse, Craig and Schoenherr, Christina and Treanor-Taylor, Mairi and Healy, Eugene and Lai, Chester and Craig, Paul and Moyes, Colin and Rickaby, William and Martin, Joanne and Proby, Charlotte and Inman, Gareth J. and Leigh, Irene 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). pp. 1159-1166. ISSN 0190-9622

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Martin, Joanne
Author

Wang, Jun and Harwood, Catherine A. and Bailey, Emma and Bewicke-Copley, Findlay and Anene, Chinedu Anthony and Thomson, Jason and Qamar, Mah Jabeen and Laban, Rhiannon and Nourse, Craig and Schoenherr, Christina and Treanor-Taylor, Mairi and Healy, Eugene and Lai, Chester and Craig, Paul and Moyes, Colin and Rickaby, William and Martin, Joanne and Proby, Charlotte and Inman, Gareth J. and Leigh, Irene 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). pp. 1159-1166. ISSN 0190-9622

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Proby, Charlotte
Author

Wang, Jun and Harwood, Catherine A. and Bailey, Emma and Bewicke-Copley, Findlay and Anene, Chinedu Anthony and Thomson, Jason and Qamar, Mah Jabeen and Laban, Rhiannon and Nourse, Craig and Schoenherr, Christina and Treanor-Taylor, Mairi and Healy, Eugene and Lai, Chester and Craig, Paul and Moyes, Colin and Rickaby, William and Martin, Joanne and Proby, Charlotte and Inman, Gareth J. and Leigh, Irene 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). pp. 1159-1166. ISSN 0190-9622

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Inman, Gareth
Author

White, Stephen E. and Schwartze, Tristin A. and Mukundan, Ananya and Schoenherr, Christina and Singh, Shashi P. and van Dinther, Maarten and Cunningham, Kyle T. and White, Madeleine P. J. and Campion, Tiffany and Pritchard, John and Hinck, Cynthia S. and ten Dijke, Peter and Inman, Gareth J. and Maizels, Rick M. and Hinck, Andrew P. (2025) TGM6 is a helminth secretory product that mimics TGF-β binding to TGFBR2 to antagonize signaling in fibroblasts. Nature Communications, 16 (1): 1847. ISSN 2041-1723

Singh, Shashi P. and Smyth, Danielle J. and Cunningham, Kyle T. and Mukundan, Ananya and Byeon, Chang-Hyeock and Hinck, Cynthia S. and White, Madeleine P.J. and Ciancia, Claire and Wąsowska, Natalia and Sanders, Anna and Jin, Regina and White, Ruby F. and Lilla, Sergio and Zanivan, Sara and Schoenherr, Christina and Inman, Gareth and van Dinther, Maarten and ten Dijke, Peter and Hinck, Andrew P. and Maizels, Rick M. (2025) The TGF-β mimic TGM4 achieves cell specificity through combinatorial surface co-receptor binding. EMBO Reports, 26 (1). pp. 218-244. ISSN 1469-221X

Smith, Craig D.L. and McMahon, Alex D. and Purkayastha, Mitana and Creaney, Grant and Clements, Kelten and Inman, Gareth J. and Bhatti, Lesley A. and Douglas, Catriona M. and Paterson, Claire and Conway, David I. (2024) Head and neck cancer incidence is rising but the sociodemographic profile is unchanging: a population epidemiological study (2001-2020). BJC Reports, 2: 71. ISSN 2731-9377

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Leigh, Irene M.
Author

Wang, Jun and Harwood, Catherine A. and Bailey, Emma and Bewicke-Copley, Findlay and Anene, Chinedu Anthony and Thomson, Jason and Qamar, Mah Jabeen and Laban, Rhiannon and Nourse, Craig and Schoenherr, Christina and Treanor-Taylor, Mairi and Healy, Eugene and Lai, Chester and Craig, Paul and Moyes, Colin and Rickaby, William and Martin, Joanne and Proby, Charlotte and Inman, Gareth J. and Leigh, Irene 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). pp. 1159-1166. ISSN 0190-9622

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