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
AI Summary:
A 20-gene signature was developed and validated to predict primary cutaneous squamous cell carcinoma (cSCC) metastatic risk. The signature showed high accuracy, sensitivity, specificity, and positive predictive value.AI Topics:
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.
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
See full publications listHarwood, 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
See full publications listBailey, 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
See full publications listBewicke-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
See full publications listAnene, 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
See full publications listThomson, 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
See full publications listQamar, 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
See full publications listLaban, 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
See full publications listNourse, 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
See full publications listSchoenherr, 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
See full publications listTreanor-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
See full publications listHealy, 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
See full publications listLai, 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
See full publications listCraig, 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
See full publications listMoyes, 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
See full publications listRickaby, 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
See full publications listMartin, 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
See full publications listProby, 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
See full publications listInman, 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
See full publications listLeigh, 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
See full publications listAvailable under License Creative Commons Attribution Non-commercial No Derivatives.
Download (477kB) | Preview