Li Tianhao, Wang Liquan, Yu Nanze, Zeng Ang, Huang Jiuzuo, Long Xiao
Department of Plastic and Cosmetic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Front Oncol. 2023 Jan 11;12:1055308. doi: 10.3389/fonc.2022.1055308. eCollection 2022.
Dysregulation of cell cycle progression (CCP) is a trait that distinguishes cancer from other diseases. In several cancer types, CCP-related genes serve as the primary risk factor for prognosis, but their role in cutaneous melanoma remains unclear.
Data from cutaneous melanoma patients were acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Using a Wilcoxon test, the level of CCP-related gene expression in cutaneous melanoma patient tissues was compared to that in normal skin tissues. Logistic analysis was then utilized to calculate the connection between the CCP-related genes and clinicopathological variables. The important functions of the CCP-related genes were further investigated using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and single-sample Gene Set Enrichment Analysis (ssGSEA). Univariate and multivariate Cox analyses and Kaplan-Meier analysis were used to estimate the association between CCP-related genes and prognosis. In addition, using Cox multivariate analysis, a nomogram was constructed to forecast the influence of CCP-related genes on survival rates.
High expression of CCP-related genes was associated with TNM stage, age, pathological grade, and Breslow depth (P < 0.05). Multivariate analysis demonstrated that CCP-related genes were an independent factor in overall survival and disease-specific survival. High levels of gene expression originating from CCP were shown by GSEA to trigger DNA replication, the G1-S specific transcription factor, the mitotic spindle checkpoint, and the cell cycle. There was a negative association between CCP-related genes and the abundance of innate immune cells. Finally, we revealed that knockdown of cell division cycle-associated gene 3 (CDCA3) significantly suppressed the proliferation and migration ability of cutaneous melanoma cells.
According to this study, CCP-related genes could serve as potential biomarkers to assess the prognosis of cutaneous melanoma patients and are crucial immune response regulators.
细胞周期进程（CCP）失调是癌症区别于其他疾病的一个特征。在几种癌症类型中，CCP相关基因是预后的主要风险因素，但其在皮肤黑色素瘤中的作用仍不清楚。
从癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）获取皮肤黑色素瘤患者的数据。使用Wilcoxon检验，将皮肤黑色素瘤患者组织中CCP相关基因的表达水平与正常皮肤组织中的表达水平进行比较。然后利用逻辑分析计算CCP相关基因与临床病理变量之间的关联。使用基因本体论（GO）、京都基因与基因组百科全书（KEGG）通路分析和单样本基因集富集分析（ssGSEA）进一步研究CCP相关基因的重要功能。使用单因素和多因素Cox分析以及Kaplan-Meier分析来评估CCP相关基因与预后之间的关联。此外，通过Cox多因素分析构建了一个列线图，以预测CCP相关基因对生存率的影响。
CCP相关基因的高表达与TNM分期、年龄、病理分级和Breslow深度相关（P < 0.05）。多因素分析表明，CCP相关基因是总生存和疾病特异性生存的独立因素。基因集富集分析（GSEA）显示，源自CCP的高水平基因表达会触发DNA复制、G1-S特异性转录因子、有丝分裂纺锤体检查点和细胞周期。CCP相关基因与先天免疫细胞的丰度之间存在负相关。最后，我们发现敲低细胞分裂周期相关基因3（CDCA3）可显著抑制皮肤黑色素瘤细胞的增殖和迁移能力。
根据本研究，CCP相关基因可作为评估皮肤黑色素瘤患者预后的潜在生物标志物，并且是关键的免疫反应调节因子。
