Ou Wei, Zhou Jiang, Huang Zhenhua, Yang XinLiang, Liu Xiaohong, Zuo Wenjian, Luo ZhiYong, Su Min
Department of Biochemistry and Molecular Biology, School of Life Sciences, Central South University, Changsha 410008, China.
Department of Pharmacy, Yueyang Central Hospital, Yueyang 414000, China.
J Cancer. 2025 Aug 11;16(12):3752-3766. doi: 10.7150/jca.117471. eCollection 2025.
: Skin cutaneous melanoma (SKCM) is a malignant tumor characterized by aggressive invasion and a high tendency for metastasis. This study explores the potential of MCM4 as a biomarker for SKCM and its impact on the tumor microenvironment (TME). : A comprehensive analysis of MCM4 was conducted using public databases to characterize the expression, genomic alterations, and clinical significance of MCM4 in pan-cancer, including SKCM. Bioinformatics tools were employed to identify upstream regulators of MCM4. The functional mechanisms of MCM4 in SKCM were explored through correlation, differential, and enrichment analyses. Immune infiltration and drug sensitivity were assessed to understand the role of MCM4 in the TME and its potential therapeutic implications. Functional experiments were performed in A375 and SK-MEL-28 cells. : MCM4 were significantly upregulated in tumors. Survival curves indicated that patients with high MCM4 expression had poor survival advantage. SRF was identified as a potential transcription factor regulating MCM4. Functional enrichment revealed a positive correlation between MCM4 and cell cycle-related pathways, and a negative correlation with immune effector process-related pathways. High MCM4 expression was associated with "cold" tumor characteristics. Immunotherapy response analysis demonstrated higher response rates in patients with low MCM4 expression. Drug sensitivity analysis suggested potential therapeutic drug options based on MCM4 expression. Functional experiments confirmed the oncogenesis effects of MCM4 in SKCM cells. : MCM4 is a potential prognostic biomarker and predictor of immunotherapy response in SKCM patients.
皮肤黑色素瘤（SKCM）是一种恶性肿瘤，其特征是侵袭性强且转移倾向高。本研究探讨了MCM4作为SKCM生物标志物的潜力及其对肿瘤微环境（TME）的影响。：利用公共数据库对MCM4进行了全面分析，以表征MCM4在包括SKCM在内的泛癌中的表达、基因组改变和临床意义。采用生物信息学工具鉴定MCM4的上游调节因子。通过相关性、差异性和富集分析探讨了MCM4在SKCM中的功能机制。评估免疫浸润和药物敏感性，以了解MCM4在TME中的作用及其潜在的治疗意义。在A375和SK-MEL-28细胞中进行了功能实验。：MCM4在肿瘤中显著上调。生存曲线表明，MCM4表达高的患者生存优势较差。SRF被确定为调节MCM4的潜在转录因子。功能富集显示MCM4与细胞周期相关途径呈正相关，与免疫效应过程相关途径呈负相关。MCM4高表达与“冷”肿瘤特征相关。免疫治疗反应分析表明，MCM4表达低的患者反应率更高。药物敏感性分析基于MCM4表达提出了潜在的治疗药物选择。功能实验证实了MCM4在SKCM细胞中的致癌作用。：MCM4是SKCM患者潜在的预后生物标志物和免疫治疗反应预测指标。
