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宫颈癌干性相关枢纽基因的鉴定与验证:一项生物信息学与实验研究

英文原题:Identification and validation of stemness-associated hub genes in cervical cancer: a bioinformatics and experimental study.

查看英文原题

Identification and validation of stemness-associated hub genes in cervical cancer: a bioinformatics and experimental study.

PubMed 2026/06/27(内容时间) World J Surg Oncol Q1 · IF 2.8(JCR 2025)

研究概要

通过文献挖掘和CellMarker 2.0,我们识别出1345个与干性相关的基因,这些基因与TCGA-CESC数据集中的差异表达基因(DEGs)重叠(log2FC > 2,p < 0.05),从而得到216个与干性相关的DEGs。

中文摘要

癌症干细胞(CSCs)是具有自我更新和分化能力的亚群,驱动宫颈癌(CC)患者的进展、复发和治疗耐药。然而,维持CC干性的完整基因集仍未完全明确。我们旨在鉴定关键的干性相关基因,并评估其预后价值、免疫关联和药物敏感性。通过文献挖掘和CellMarker 2.0,我们鉴定了1345个干性相关基因,这些基因与TCGA-CESC数据集的差异表达基因(DEGs)重叠(log2FC > 2,p < 0.05),得到216个干性相关DEGs。蛋白质-蛋白质相互作用网络(STRING)和CytoHubba(MCC算法)揭示了十个枢纽基因(HGs):CCNB1、CCNA2、BUB1B、UBE2C、KIF11、CCNB2、KIF23、CDC20、CDC6和FOXM1。基因本体和KEGG分析显示主要富集于细胞周期进程。Cox回归和Kaplan-Meier分析确定BUB1B、CCNA2、CDC20、FOXM1和KIF23为不良总生存期的风险因素,其中KIF11成为独立预后因素。HGs过表达与15种免疫细胞类型的浸润改变显著相关,包括与CD8 + T细胞和NK细胞的负相关。我们鉴定了661种靶向这些HGs的独特药物/化学物质,包括FDA批准的再利用药物。通过RT-PCR的实验验证证实,与正常样本相比,FOXM1和KIF11在CC组织和细胞系中显著过表达。这些干性相关HGs,特别是FOXM1和KIF11,可能作为潜在的预后生物标志物和治疗靶点,值得进一步研究干性驱动的CC进展。

展开英文摘要原文

Cancer stem cells (CSCs) are a subpopulation with self-renewal and differentiation capacity that drive the progression, recurrence, and therapeutic resistance of patients with cervical cancer (CC). However, the complete set of genes that maintain stemness in CC remains incompletely defined. We aimed to identify key stemness-related genes and evaluate their prognostic utility, immune associations, and drug sensitivity. Through literature mining and CellMarker 2.0, we identified 1345 stemness-associated genes that overlapped with differentially expressed genes (DEGs) from the TCGA-CESC dataset (log2FC > 2, p < 0.05), yielding 216 stemness-related DEGs. A protein-protein interaction network (STRING) and CytoHubba (MCC algorithm) revealed ten hub genes (HGs): CCNB1, CCNA2, BUB1B, UBE2C, KIF11, CCNB2, KIF23, CDC20, CDC6, and FOXM1. Gene ontology and KEGG analyses revealed predominant enrichment in cell cycle progression. Cox regression and Kaplan‒Meier analyses identified BUB1B, CCNA2, CDC20, FOXM1, and KIF23 as risk factors for poor overall survival, with KIF11 emerging as an independent prognostic factor. HGs overexpression significantly correlated with altered infiltration of 15 immune cell types, including negative associations with CD8 + T and NK cells. We identified 661 unique drugs/chemicals targeting these HGs, including FDA-approved repurposed agents. Experimental validation via RT‒PCR confirmed significant overexpression of FOXM1 and KIF11 in CC tissues and cell lines compared with normal samples. These stemness-associated HGs, particularly FOXM1 and KIF11, may serve as potential prognostic biomarkers and therapeutic targets, warranting further investigation of stemness-driven CC progression.

论文信息

作者
Kabekkodu SP、Rodrigues AF、Hebbar P、Bhat S
第一作者单位
Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, India.India
通讯作者单位
Department of Biotherapeutics Research, Manipal Academy of Higher Education, Manipal, India. samatha.bhat@manipal.edu.India
期刊
World journal of surgical oncology2026 Jun 27
原文标识
PubMed 42365339 · DOI 10.1186/s12957-026-04472-7