Qi Jiayue, Guo Qingqing, Bai Jia, Liang Xiaoqiang, Zhu Wenwei, Li Chengxin, Xie Fang
Department of Dermatology, First Medical Center, Chinese PLA General Hospital, Beijing, People's Republic of China.
School of Medicine, Nankai University, Tianjin, People's Republic of China.
Onco Targets Ther. 2024 Oct 26;17:841-856. doi: 10.2147/OTT.S468399. eCollection 2024.
Cutaneous squamous cell carcinoma (cSCC) ranks as the second most common malignancy in clinical practice and poses a significant threat to public health due to its high malignancy. In this study, we aimed to explore potential biomarkers and molecular mechanisms of cSCC.
Differentially expressed genes (DEGs) from GSE66359 and GSE117247 datasets were identified using R software. We conducted enrichment analyses and screened hub genes through protein-protein interaction (PPI) analysis and weighted gene co-expression network analysis (WGCNA). To assess the diagnostic performance of these genes, we generated ROC curves using both internal and external datasets (GSE45164) and validated the expression levels of these genes in cSCC tissues through immunohistochemistry. Subsequently, we predicted the target miRNAs and lncRNAs for hub genes using online databases and constructed competing endogenous RNA (ceRNA) networks.
In total, we identified 505 upregulated DEGs and 522 downregulated DEGs. Through PPI and WGCNA analyses, we identified four hub genes exhibiting robust diagnostic performance in internal and external datasets (AUC > 0.9) and selected three previously unreported genes for further analysis. Immunohistochemistry demonstrated significantly elevated CCNA2, CCNB2, and UBE2C expression in cSCC tissues compared to normal skin tissues. Finally, we constructed three ceRNA networks, namely NEAT1/H19-hsa-miR-148a-3p-CCNA2 and NEAT1-hsa-miR-140-3p-UBE2C.
In conclusion, we have identified CCNA2, CCNB2, and UBE2C as novel biomarkers for cSCC, and the NEAT1/H19-hsa-miR-148a-3p-CCNA2 and NEAT1-hsa-miR-140-3p-UBE2C ceRNA networks may represent molecular mechanisms under-lying cSCC progression. The findings of this study offer new diagnostic and therapeutic options for cSCC patients.
皮肤鳞状细胞癌（cSCC）是临床实践中第二常见的恶性肿瘤，因其高恶性对公众健康构成重大威胁。在本研究中，我们旨在探索cSCC的潜在生物标志物和分子机制。
使用R软件从GSE66359和GSE117247数据集中鉴定差异表达基因（DEG）。我们进行了富集分析，并通过蛋白质-蛋白质相互作用（PPI）分析和加权基因共表达网络分析（WGCNA）筛选枢纽基因。为评估这些基因的诊断性能，我们使用内部和外部数据集（GSE45164）生成ROC曲线，并通过免疫组织化学验证这些基因在cSCC组织中的表达水平。随后，我们使用在线数据库预测枢纽基因的靶标miRNA和lncRNA，并构建竞争性内源RNA（ceRNA）网络。
我们总共鉴定出505个上调的DEG和522个下调的DEG。通过PPI和WGCNA分析，我们鉴定出四个在内部和外部数据集中表现出强大诊断性能的枢纽基因（AUC>0.9），并选择了三个以前未报道的基因进行进一步分析。免疫组织化学显示，与正常皮肤组织相比，cSCC组织中CCNA2、CCNB2和UBE2C的表达显著升高。最后，我们构建了三个ceRNA网络，即NEAT1/H19-hsa-miR-148a-3p-CCNA2和NEAT1-hsa-miR-140-3p-UBE2C。
总之，我们已将CCNA2、CCNB2和UBE2C鉴定为cSCC的新型生物标志物，并且NEAT1/H19-hsa-miR-148a-3p-CCNA2和NEAT1-hsa-miR-140-3p-UBE2C ceRNA网络可能代表cSCC进展的分子机制。本研究结果为cSCC患者提供了新的诊断和治疗选择。
