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Article Open Access

Identification of cancer‑associated fibroblast biomarkers in cutaneous squamous cell carcinoma

  • Authors:
    • Yuanyuan Deng
    • Jue Qi
    • Yu Tang
    • Yueting Cun
    • Qian He
    • Li He
  • View Affiliations / Copyright

    Affiliations: Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China, Yunnan Key Laboratory of Breast Cancer Precision Medicine, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital, Kunming, Yunnan 650118, P.R. China, Department of Dermatology, Chuxiong People's Hospital, Chuxiong, Yunnan 675000, P.R. China, Institute of Biomedical Engineering of Kunming Medical University, Kunming, Yunnan 650032, P.R. China
    Copyright: © Deng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 514
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    Published online on: September 17, 2026
       https://doi.org/10.3892/ol.2026.15869
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Abstract

Cancer‑associated fibroblasts (CAFs) are a key component of the tumor microenvironment and serve key roles in tumor progression, extracellular matrix remodeling and immune modulation. Nevertheless, no consensus has been reached thus far on biomarkers for CAFs in cutaneous squamous cell carcinoma (cSCC), a situation that hinders mechanistic research into this disease. In the present study, large‑scale datasets were used to independently screen for candidate CAF biomarkers and subsequently validate their authenticity at the tissue level in cSCC specimens, including those derived from actinic keratosis (AK). Microarray datasets (GSE139505 and GSE191334) from the Gene Expression Omnibus database were analyzed to identify differentially expressed genes (DEGs) in cSCC tissues compared with normal skin tissues. These DEGs were then intersected with cSCC‑associated genes retrieved from GeneCards and a set of 50 previously identified CAF marker genes. The expression of candidate genes was further validated in cSCC tissue samples and normal skin samples by immunohistochemistry. To gain further insight into the changes of these candidate genes across different stages of cSCC progression, AK samples were also incorporated during validation using multiplex immunofluorescence technology. Enrichment analysis revealed that the overlapping genes were primarily involved in the MAPK signaling pathway, PI3K‑Akt signaling pathway and extracellular matrix organization. A total of five genes, melanoma cell adhesion molecule (MCAM), actin α2, smooth muscle (ACTA2), transgelin (TAGLN), platelet derived growth factor receptor β (PDGFRB) and regulator of G protein signaling 5 (RGS5), were revealed to be significantly upregulated in cSCC compared with normal skin. Among these, MCAM stood out from the cross‑analysis pipeline, whereas ACTA2, TAGLN, RGS5 and PDGFRB were CAF markers identified based on single‑cell literature studies. The five genes (MCAM, ACTA2, TAGLN, PDGFRB and RGS5), can serve as candidate biomarkers for CAFs, facilitating their identification and definition. This provides a useful reference for further investigation into the contribution of CAF in the progression of cSCC.
View Figures

Figure 1

Overlapping genes among three sets
and their functional enrichment. (A) Venn diagram of two Gene
Expression Omnibus datasets and one GeneCards dataset. (B) Kyoto
Encyclopedia of Genes and Genomes enrichment analysis of
differentially expressed genes. ECM, extracellular matrix;
AGE-RAGE, advanced glycation end-products-receptor for advanced
glycation end-products.

Figure 2

PPI network analysis results. (A)
Display of MCODE analysis module genes. (B) Kyoto Encyclopedia of
Genes and Genomes enrichment analysis of MCODE module genes and
CytoHubba MCC TOP 20 genes. (C) Display of CytoHubba Maximum Clique
Centrality Top 20 genes.

Figure 3

Candidate gene identification. (A)
Intersection of DEGs and CAFs from the cSCC single-cell study. (B)
Immunohistochemical analysis statistics of MCAM in cSCC and normal
samples. (C) Immunohistochemical analysis statistics of ACTA2,
TAGLN, RGS5 and PDGFRB in cSCC and NL. *P<0.05 and **P<0.01.
(D) Results of multiplex immunofluorescence for NL, AK and cSCC.
Magnification, ×40. CAFs, cancer-associated fibroblast markers;
cSCC, cutaneous squamous cell carcinoma; NL, normal skin; AK,
actinic keratosis; MCAM, melanoma cell adhesion molecule; of ACTA2,
actin α2 smooth muscle; TAGLN, transgelin; RGS5, regulator of G
protein signaling 5 and PDGFRB, platelet derived growth factor
receptor β; DEGs, differentially expressed genes.
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Copy and paste a formatted citation
Spandidos Publications style
Deng Y, Qi J, Tang Y, Cun Y, He Q and He L: Identification of cancer‑associated fibroblast biomarkers in cutaneous squamous cell carcinoma. Oncol Lett 32: 514, 2026.
APA
Deng, Y., Qi, J., Tang, Y., Cun, Y., He, Q., & He, L. (2026). Identification of cancer‑associated fibroblast biomarkers in cutaneous squamous cell carcinoma. Oncology Letters, 32, 514. https://doi.org/10.3892/ol.2026.15869
MLA
Deng, Y., Qi, J., Tang, Y., Cun, Y., He, Q., He, L."Identification of cancer‑associated fibroblast biomarkers in cutaneous squamous cell carcinoma". Oncology Letters 32.5 (2026): 514.
Chicago
Deng, Y., Qi, J., Tang, Y., Cun, Y., He, Q., He, L."Identification of cancer‑associated fibroblast biomarkers in cutaneous squamous cell carcinoma". Oncology Letters 32, no. 5 (2026): 514. https://doi.org/10.3892/ol.2026.15869
Copy and paste a formatted citation
x
Spandidos Publications style
Deng Y, Qi J, Tang Y, Cun Y, He Q and He L: Identification of cancer‑associated fibroblast biomarkers in cutaneous squamous cell carcinoma. Oncol Lett 32: 514, 2026.
APA
Deng, Y., Qi, J., Tang, Y., Cun, Y., He, Q., & He, L. (2026). Identification of cancer‑associated fibroblast biomarkers in cutaneous squamous cell carcinoma. Oncology Letters, 32, 514. https://doi.org/10.3892/ol.2026.15869
MLA
Deng, Y., Qi, J., Tang, Y., Cun, Y., He, Q., He, L."Identification of cancer‑associated fibroblast biomarkers in cutaneous squamous cell carcinoma". Oncology Letters 32.5 (2026): 514.
Chicago
Deng, Y., Qi, J., Tang, Y., Cun, Y., He, Q., He, L."Identification of cancer‑associated fibroblast biomarkers in cutaneous squamous cell carcinoma". Oncology Letters 32, no. 5 (2026): 514. https://doi.org/10.3892/ol.2026.15869
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