Mesh : Kinesins / genetics metabolism Humans Animals Adenocarcinoma of Lung / genetics drug therapy pathology metabolism Mice Lung Neoplasms / genetics drug therapy pathology Epithelial-Mesenchymal Transition / genetics Prognosis Gene Expression Regulation, Neoplastic Cell Proliferation / genetics Biomarkers, Tumor / genetics Cell Line, Tumor Cell Movement / genetics Gene Expression Profiling Xenograft Model Antitumor Assays

来  源:   DOI:10.1039/d4mo00044g

Abstract:
Objective: this study evaluates the prognostic relevance of gene subtypes and the role of kinesin family member 2C (KIF2C) in lung cancer progression. Methods: high-expression genes linked to overall survival (OS) and progression-free interval (PFI) were selected from the TCGA-LUAD dataset. Consensus clustering analysis categorized lung adenocarcinoma (LUAD) patients into two subtypes, C1 and C2, which were compared using clinical, drug sensitivity, and immunotherapy analyses. A random forest algorithm pinpointed KIF2C as a prognostic hub gene, and its functional impact was assessed through various assays and in vivo experiments. Results: The study identified 163 key genes and distinguished two LUAD subtypes with differing OS, PFI, pathological stages, drug sensitivity, and immunotherapy response. KIF2C, highly expressed in the C2 subtype, was associated with poor prognosis, promoting cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), with knockdown reducing tumor growth in mice. Conclusion: The research delineates distinct LUAD subtypes with significant clinical implications and highlights KIF2C as a potential therapeutic target for personalized treatment in LUAD.
摘要:
目的:本研究评估基因亚型的预后相关性以及驱动蛋白家族成员2C(KIF2C)在肺癌进展中的作用。方法:从TCGA-LUAD数据集中选择与总生存期(OS)和无进展间隔(PFI)相关的高表达基因。共识聚类分析将肺腺癌(LUAD)患者分为两种亚型,C1和C2,使用临床比较,药物敏感性,和免疫疗法分析。随机森林算法将KIF2C确定为预后中心基因,并通过各种测定和体内实验评估其功能影响。结果:该研究鉴定了163个关键基因,并区分了两种OS不同的LUAD亚型。PFI,病理阶段,药物敏感性,和免疫疗法反应。KIF2C,在C2亚型中高度表达,与不良预后有关,促进癌细胞增殖,迁移,入侵,和上皮-间质转化(EMT),降低小鼠的肿瘤生长。结论:该研究描述了具有重要临床意义的不同LUAD亚型,并强调KIF2C是LUAD个性化治疗的潜在治疗靶标。
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