Zhou Jianhua, Xu Zhuxian, Yu Yang, Zhu Bingye, Xing Qianwei
Department of Urology, Affiliated Hospital of Nantong University, No. 20 West Temple Road, Nantong, 226001, Jiangsu, China.
Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China.
Discov Oncol. 2025 Apr 28;16(1):626. doi: 10.1007/s12672-025-02438-x.
In the development of several cancers, the Forkhead Box M1 (FOXM1) is crucial. The relationship between the immune system and FOXM1 in renal cell carcinoma (ccRCC), which has been verified by bulk RNA sequencing and scRNA sequencing, is the primary subject of this research.
Publicly available data related to FOXM1 and ccRCC were extracted from The Cancer Genome Atlas (TCGA) database. The impact of FOXM1 on the prognosis of ccRCC was examined using Cox regression analysis. Results were verified by immunohistochemistry and quantitative real-time PCR (qRT-PCR). Additionally, single-cell sequencing data were analyzed.
When compared to para-carcinoma tissues, the expression of FOXM1 was considerably higher in ccRCC tissues. Patients with elevated FOXM1 expression had lower survival rates. FOXM1 may be a standalone prognostic factor for ccRCC, according to results of univariate and multivariate Cox regression studies. Reduced FOXM1 expression was linked to higher immunotherapy sensitivity, according to immunocorrelation analysis. This suggests FOXM1 may mediate immunotherapy resistance in ccRCC. Additionally, FOXM1 showed strong associations with tumor mutation load, microsatellite instability, and antitumor immunity. These results imply FOXM1 may regulate antitumor immunity in the ccRCC microenvironment. Consistent results from immunohistochemistry, PCR, and single-cell RNA sequencing confirmed upregulated FOXM1 expression in ccRCC.
According to the findings, FOXM1 might be used as a stand-alone prognostic biomarker for ccRCC. Moreover, FOXM1 has exhibited robust correlations with microsatellite instability, tumor mutation burden, immune response, and immunotherapy efficacy. FOXM1 may promote ccRCC pathogenesis partly by suppressing antitumor immunity and mediating immunotherapy resistance.
在几种癌症的发展过程中，叉头框M1（FOXM1）至关重要。本研究的主要主题是通过批量RNA测序和单细胞RNA测序验证的肾细胞癌（ccRCC）中免疫系统与FOXM1之间的关系。
从癌症基因组图谱（TCGA）数据库中提取与FOXM1和ccRCC相关的公开数据。使用Cox回归分析检查FOXM1对ccRCC预后的影响。结果通过免疫组织化学和定量实时PCR（qRT-PCR）进行验证。此外，还分析了单细胞测序数据。
与癌旁组织相比，ccRCC组织中FOXM1的表达明显更高。FOXM1表达升高的患者生存率较低。单因素和多因素Cox回归研究结果表明，FOXM1可能是ccRCC的独立预后因素。免疫相关性分析表明，FOXM1表达降低与更高的免疫治疗敏感性相关。这表明FOXM1可能介导ccRCC中的免疫治疗耐药性。此外，FOXM1与肿瘤突变负荷、微卫星不稳定性和抗肿瘤免疫密切相关。这些结果表明FOXM1可能调节ccRCC微环境中的抗肿瘤免疫。免疫组织化学、PCR和单细胞RNA测序的一致结果证实了ccRCC中FOXM1表达上调。
根据研究结果，FOXM1可能用作ccRCC的独立预后生物标志物。此外，FOXM1与微卫星不稳定性、肿瘤突变负担、免疫反应和免疫治疗疗效密切相关。FOXM1可能部分通过抑制抗肿瘤免疫和介导免疫治疗耐药性来促进ccRCC的发病机制。
