结肠腺癌中二硫中毒相关基因的预后和治疗潜力:一项全面的多组学研究。

IF 5.3 2区 医学 Q1 ONCOLOGY
Ye Song, Haoran Zhu, Junyang Wei, Shanxue Yin
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引用次数: 0

摘要

背景:二硫中毒相关基因(DRGs)在结肠癌(CC)的预后中起着关键作用,并有望成为潜在的治疗靶点。本研究系统地评估了它们的预后意义,并探讨了它们在结肠腺癌治疗干预中的潜力。方法:基于DRG表达对结肠腺癌(COAD)样本进行分类,分析不同分子亚型间免疫景观的差异。研究了高风险(HRG)和低风险(LRG)组之间的差异以及不同阶段细胞群体动态的变化。在T细胞发育过程中,我们评估了透明膜相关双甲素1 (DIAPH1)和NADH:泛醌氧化还原酶亚基B10 (NDUFB10)的表达模式,这是预后模型的关键组成部分。该模型使用外部数据集进行验证,并进行单细胞分析以研究肿瘤浸润细胞群体的空间分布差异。结果:DRGs在COAD患者T细胞分化调控中起关键作用。在T细胞发育过程中,DIAPH1和NDUFB10表现出显著的波动,表明它们参与免疫调节。单细胞分析显示T细胞和上皮细胞之间存在明显的空间分布模式。ProjecTILs算法鉴定出更高比例的Th1细胞,而图卷积网络(GCN)分析显示,不同表型的T细胞亚型比例没有显著差异。体外实验进一步证明,在T细胞中敲低DIAPH1和NDUFB10可有效抑制肿瘤增殖。结论:基于DRGs的预后模型对COAD具有较强的预测能力,突出了DRGs作为治疗靶点的潜力。这些发现为开发针对CC中二硫化物下垂途径的新治疗策略提供了坚实的基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Prognostic and therapeutic potential of disulfidptosis-related genes in colon adenocarcinoma: a comprehensive multi-omics study.

Background: Disulfidptosis-related genes (DRGs) have emerged as key players in the prognosis of colon cancer(CC) and hold promise as potential therapeutic targets. This study systematically evaluates their prognostic significance and explores their potential for therapeutic intervention in colon adenocarcinoma.

Methods: Colon adenocarcinoma(COAD) samples were categorized based on DRG expression to analyze differences in the immune landscape across molecular subtypes. Variations between high-risk (HRG) and low-risk (LRG) groups and changes in cell population dynamics across different stages were examined. The expression patterns of Diaphanous-Related Formin 1 (DIAPH1) and NADH: Ubiquinone Oxidoreductase Subunit B10 (NDUFB10), key components of the prognostic model, were assessed during T cell development. The model was validated using external datasets, and single-cell analysis was performed to investigate spatial distribution differences in tumor-infiltrating cell populations.

Results: DRGs were critical in modulating T cell differentiation in COAD. DIAPH1 and NDUFB10 showed significant fluctuations during T cell development, indicating their involvement in immune regulation. Single-cell analysis revealed distinct spatial distribution patterns between T cells and epithelial cells. The ProjecTILs algorithm identified a higher proportion of Th1 cells, while Graph Convolutional Network (GCN) analysis showed no significant differences in T cell subtype proportions across different phenotypes. In vitro experiments further demonstrated that the knockdown of DIAPH1 and NDUFB10 in T cells effectively inhibited tumor proliferation.

Conclusion: The DRG-based prognostic model demonstrated strong predictive power in COAD, highlighting the potential of DRGs as therapeutic targets. These findings provide a solid foundation for developing novel treatment strategies targeting disulfide ptosis pathways in CC.

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来源期刊
CiteScore
10.90
自引率
1.70%
发文量
360
审稿时长
1 months
期刊介绍: Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.
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