Hao Wende, Wang Zhenjun, Ma Huachong
Department of Emergency Abdominal Surgery, Beijing Chaoyang Hospital, Capital Medical University, No.8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing 100020, China.
Department of General Surgery, Beijing Chaoyang Hospital, Capital Medical University, No.8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing 100020, China.
Glob Med Genet. 2025 Jul 15;12(4):100067. doi: 10.1016/j.gmg.2025.100067. eCollection 2025 Dec.
Cancer stem cells (CSCs) drive colorectal cancer (CRC) progression, metastasis, and therapy resistance, but their heterogeneity limits targeted treatment efficacy. Clarifying the stemness landscape and underlying mechanisms is crucial for developing effective CRC therapies.
By integrating 10 ×single-cell data from GSE201348 and GSE161277, we constructed a single-cell atlas of nine primary CRC samples. CSCs were identified via scRNA-seq analyses. Using integrative bioinformatics tools, we identified ENY2 as a stemness-related marker and explored its potential role in CRC. We further compared genetic variants, immune infiltration, and drug sensitivity between high and low ENY2 expression groups.
Stem cell clusters (M0 and M7) in CRC were identified based on copy number variation, pseudotime trajectory, and CytoTRACE analyses. By integrating marker gene profiles, DEGs from GSE33113, CytoTRACE-based CSC genes, and prognostic genes from GSE17536, we identified two key stemness-related markers: ENY2 and PKM. ENY2 was prioritized for further analysis due to its limited investigation in CRC. Bioinformatic analyses revealed that ENY2 was significantly upregulated and associated with poor prognosis. Enrichment analyses indicated its involvement in MYC and E2F targets, G2M checkpoint, and EMT pathways. Drug sensitivity prediction suggested that high ENY2 expression may confer responsiveness to 5-fluorouracil, capecitabine, oxaliplatin, and 24 other potential agents.
ENY2 may act as a key CSC-associated biomarker that promotes CRC tumorigenesis and metastasis via the EMT pathway, which enhance our understanding of CRC pathogenesis and highlight ENY2 as a potential target for diagnosis and therapy.
癌症干细胞（CSCs）驱动结直肠癌（CRC）的进展、转移和治疗抗性，但其异质性限制了靶向治疗的疗效。阐明干性格局和潜在机制对于开发有效的CRC治疗方法至关重要。
通过整合来自GSE201348和GSE161277的10×单细胞数据，我们构建了9个原发性CRC样本的单细胞图谱。通过scRNA-seq分析鉴定CSCs。使用综合生物信息学工具，我们将ENY2鉴定为与干性相关的标志物，并探索其在CRC中的潜在作用。我们进一步比较了高ENY2表达组和低ENY2表达组之间的基因变异、免疫浸润和药物敏感性。
基于拷贝数变异、伪时间轨迹和CytoTRACE分析，在CRC中鉴定出干细胞簇（M0和M7）。通过整合标记基因谱、来自GSE33113的差异表达基因、基于CytoTRACE的CSC基因以及来自GSE17536的预后基因，我们鉴定出两个关键的与干性相关的标志物：ENY2和PKM。由于ENY2在CRC中的研究有限，因此优先对其进行进一步分析。生物信息学分析表明，ENY2显著上调且与不良预后相关。富集分析表明它参与了MYC和E2F靶点、G2M检查点和EMT途径。药物敏感性预测表明，高ENY2表达可能使细胞对5-氟尿嘧啶、卡培他滨、奥沙利铂和其他24种潜在药物产生反应。
ENY2可能作为一种关键的与CSC相关的生物标志物，通过EMT途径促进CRC的肿瘤发生和转移，这增强了我们对CRC发病机制的理解，并突出了ENY2作为诊断和治疗的潜在靶点。
