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鉴定FOXM1作为结直肠癌进展的新型蛋白质生物标志物和治疗靶点:来自免疫浸润和生物信息学分析的证据。

Identification of FOXM1 as a novel protein biomarker and therapeutic target for colorectal cancer progression: Evidence from immune infiltration and bioinformatic analyses.

作者信息

Natarajan Sathan Raj, Krishnamoorthy Rajapandiyan, Alshuniaber Mohammad A, Al-Anazi Khalid Mashay, Farah Mohammad Abul, Rajagopal Ponnulakshmi, Palanisamy Chella Perumal, Veeraraghavan Vishnu Priya, Jayaraman Selvaraj

机构信息

Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College & Hospitals, Saveetha Institute of Medical & Technical Sciences, Saveetha University, Chennai 600077, India.

Department of Food Science and Nutrition, College of Food and Agriculture Sciences, King Saud University, Riyadh 11451, Saudi Arabia.

出版信息

Int J Biol Macromol. 2024 Dec;282(Pt 4):137201. doi: 10.1016/j.ijbiomac.2024.137201. Epub 2024 Nov 1.

DOI:10.1016/j.ijbiomac.2024.137201
PMID:39489237
Abstract

Colorectal cancer (CRC) remains a major global health challenge, with its underlying molecular mechanisms, particularly the role of FOXM1, not yet fully understood. This study employed an integrated approach combining bioinformatics along with experimental validation to explore the role of FOXM1 in CRC. Using advanced computational tools and experimental techniques, we aimed to clarify the biological significance of FOXM1 and its potential impact on CRC progression and treatment. Bioinformatic analyses, including pan-cancer views, mRNA expression analysis, immune infiltrations, pathway enrichment, and functional annotations, highlighted the oncogenic potential of FOXM1 in CRC. Protein and gene expression analyses (western blot and qPCR) were conducted in HCT-116 and HT-29 cells. Platforms like GEPIA and UALCAN confirmed the diagnostic relevance of FOXM1, showing upregulated mRNA expression across various stages and metastasis. The influence of FOXM1 on immune cells, particularly CD4+, CD8+, and B cells, was significant, as revealed by immunohistochemistry. Protein-protein interaction analysis through STRING and CYTOSCAPE identified genes closely linked to FOXM1 in CRC. KEGG pathway enrichment suggested FOXM1's involvement in the p53 pathway, reinforcing its role in oncogenesis. Experimental validation confirmed elevated FOXM1 expression in HCT-116 and HT-29 cells. In summary, this study indicates that targeting FOXM1 could be a promising therapeutic strategy in CRC, emphasizing its importance in the molecular landscape of cancer progression.

摘要

结直肠癌(CRC)仍然是一项重大的全球健康挑战,其潜在的分子机制,尤其是FOXM1的作用,尚未完全明确。本研究采用生物信息学与实验验证相结合的综合方法,探讨FOXM1在结直肠癌中的作用。利用先进的计算工具和实验技术,我们旨在阐明FOXM1的生物学意义及其对结直肠癌进展和治疗的潜在影响。生物信息学分析,包括泛癌视角、mRNA表达分析、免疫浸润、通路富集和功能注释,突出了FOXM1在结直肠癌中的致癌潜力。在HCT-116和HT-29细胞中进行了蛋白质和基因表达分析(蛋白质免疫印迹和定量聚合酶链反应)。GEPIA和UALCAN等平台证实了FOXM1的诊断相关性,显示其在各个阶段和转移过程中mRNA表达上调。免疫组织化学显示,FOXM1对免疫细胞,尤其是CD4 +、CD8 +和B细胞有显著影响。通过STRING和CYTOSCAPE进行的蛋白质-蛋白质相互作用分析确定了与结直肠癌中FOXM1密切相关的基因。KEGG通路富集表明FOXM1参与p53通路,强化了其在肿瘤发生中的作用。实验验证证实了HCT-116和HT-29细胞中FOXM1表达升高。总之,本研究表明,靶向FOXM1可能是结直肠癌中一种有前景的治疗策略,强调了其在癌症进展分子格局中的重要性。

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