RESUMO
BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is a relatively common cancer that accounts for nearly 50% of non-melanoma skin cancer cases. However, the genotypes that are linked with poor prognosis and/or high relapse rates and pathogenic mechanisms of cSCC are not fully understood. To address these points, three gene expression datasets were analyzed to identify candidate biomarker genes in cSCC. METHODS: The GSE117247, GSE32979, and GSE98767 datasets comprising a total of 32 cSCC samples and 31 normal skin tissue samples were obtained from the National Center for Biotechnology Information Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified and underwent pathway enrichment analyses with the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG). A putative DEG protein-protein interaction (PPI) network was also established that included hub genes. The expression of CDK1, MAD2L1, BUB1 ans CDC20 were examined in the study. RESULTS: A total of 335 genes were identified, encompassing 219 found to be upregulated and 116 genes that were downregulated in cSCC, compared to normal tissue. Enriched functions of these DEGs were associated with Ephrin receptor signaling and cell division; cytosol, membrane, and extracellular exosomes; ATP-, poly(A) RNA-, and identical protein binding. We also established a PPI network comprising 332 nodes and identified KIF2C, CDC42, AURKA, MAD2L1, MYC, CDK1, FEN1, H2AFZ, BUB1, BUB1B, CKS2, CDC20, CCT2, ACTR2, ACTB, MAPK14, and HDAC1 as candidate hub genes. The expression of CDK1 are significantly higher in the cSCC tissues than that in normal skin. CONCLUSIONS: The DEGs identified in this study are potential therapeutic targets and biomarkers for cSCC. CDK1 is a gene closely related to the occurrence and development of cSCC, which may play an important role. Bioinformatics analysis shows that it is involved in the important pathway of the pathogenesis of cSCC, and may be recognized and applied as a new biomarker in the future diagnosis and treatment of cSCC.
RESUMO
BACKGROUND: Disabled homolog 2-interacting protein (DAB2IP), a Ras GTPase-activating protein, is downregulated in several cancers. Its depletion is involved in tumor cell proliferation, apoptosis, and metastasis, as well as epithelial-mesenchymal transition. The present study aimed to explore the potential role of DAB2IP in cutaneous squamous cell carcinoma (cSCC) and provide a theoretical basis for the diagnosis and targeted therapy of cSCC. METHODS: The clinicopathological features of DAB2IP expression in cSCC were analyzed by immunohistochemistry, and the effects of DAB2IP on SCL-1 cell behavior were determined via genetic interference in vitro. SCL-1 cell lines that exhibited reduced expression of DAB2IP and a scrambled shRNA control were constructed using a lentivirus vector-based shRNA technique. RNA extraction, reverse transcription-quantitative PCR (RT-qPCR), MTT assay, colony formation test, cell cycle analysis, apoptosis test, transwell assay, wound-healing assay, in vitro invasive assay were used in this study. RESULTS: The immunohistochemical results demonstrated that the expression of DAB2IP was higher in cSCC tissues than in soft fibroma. The level of DAB2IP expression was associated with the degree of malignancy and the depth of tumor infiltration; however, it had no association with patients' sex, tumor size, location, or phenotype. The results of the MTT, cell cycle, apoptosis, and invasion experiments demonstrated that knockdown of DAB2IP inhibited the viability and invasion of SCL-1 cells in vitro. CONCLUSIONS: High expression of DAB2IP may contribute to the development and proliferation of cSCC.
