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Abstract
BackgroundCutaneous squamous cell carcinoma (cSCC) often follows actinic keratosis (AK) and is the second most common skin cancer worldwide. To reduce metastasis risk, it is important to diagnose and treat cSCC early. This study aimed to identify hub genes associated with cSCC and AK.MethodsThis study used three datasets GSE45216, GSE98774, and GSE108008. We combined samples from the GSE45216 and GSE98774 datasets into the new dataset GSE45216–98774. We applied a weighted gene co-expression network analysis (WGCNA) to investigate key modules and hub genes associated with cSCC and AK. We considered the hub genes found in both the GSE45216–98774 and GSE108008 datasets as validated hub genes. We tested whether the expression of hub genes could predict patient survival outcomes in other cancers using TCGA pan-cancer data.ResultsWe identified modules most relevant to cSCC and AK. Additionally, we identified and validated seven hub genes of cSCC: GATM, ARHGEF26, PTHLH, MMP1, POU2F3, MMP10 and GATA3. We did not find validated hub genes for AK. Each hub gene was significantly associated with the survival of various cancer types. Only GATA3 was significantly associated with melanoma survival.ConclusionsWe applied WGCNA to find seven hub genes that play important roles in cSCC tumorigenesis. These results provide new insights that help explain the pathogenesis of cSCC. These hub genes may become biomarkers or therapeutic targets for accurate diagnosis and treatment of cSCC in the future.
Highlights
Cutaneous squamous cell carcinoma often follows actinic keratosis (AK) and is the second most common skin cancer worldwide
Detection of differentially expressed genes (DEGs) By comparing the Cutaneous squamous cell carcinoma (cSCC) and AK samples in the GSE45216–98774 dataset, we identified a total of 1432 DEGs (Fig. 4a and Supplementary Table 18), including 722 down-regulated genes and 710 up-regulated genes
By comparing cSCC and AK samples in the GSE108008 dataset, we identified a total of 183 DEGs (Fig. 4d and Supplementary Table 20), including 65 down-regulated genes and 118 up-regulated genes
Summary
Cutaneous squamous cell carcinoma (cSCC) often follows actinic keratosis (AK) and is the second most common skin cancer worldwide. This study aimed to identify hub genes associated with cSCC and AK. Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer after basal cell carcinoma, and in recent years has experienced increased incidence. Recent genome-wide association studies from patients identified several loci associated with cSCC, including pigmentation-related loci [2, 3]. Chen et al BMC Cancer (2021) 21:852 comparing cSCC and normal samples through differential gene expression analysis. These studies found differentially expressed genes (DEGs) involved mainly in cell division, cell cycle, apoptosis, inflammation, and epidermal differentiation [4,5,6]
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