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与迁移小体相关的基因作为结直肠癌潜在的预后和免疫治疗反应预测指标

Migrasome-Related Genes as Potential Prognosis and Immunotherapy Response Predictors for Colorectal Cancer.

作者信息

Chang Lu, Qin Chao, Chu Yimin, Guan Ming, Deng Xuan

机构信息

Department of Laboratory Medicine, Huashan Hospital Fudan University, Shanghai 200040, China.

Digestive Endoscopy Center, Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200050, China.

出版信息

Biomedicines. 2025 Mar 26;13(4):799. doi: 10.3390/biomedicines13040799.

Abstract

Studies highlight the role of migrasomes as mediators of intercellular communication and signaling, critical in influencing tumorigenesis and progression. Yet migrasome-related genes and their potential role in colorectal cancer prognosis remain unexplored. Differentially expressed gene set A (DEG set A) was identified in the TCGA-CRC dataset, and Weighted Gene Co-expression Network Analysis (WGCNA) was performed to identify the most important modules associated with migrasome-related gene (MRG) scores. Single-cell RNA-seq dataset GSE231559 DEG set B was determined. Candidate migrasome-related genes were filtered by intersecting DGE set A, key module genes, and DEG set B. Prognostic genes were subsequently screened through regression analysis, and a risk model was developed. Patients with CRC in the TCGA cohort were stratified into high- and low-risk groups based on the optimal cutoff of the risk score. Immunotherapy response-related analyses were then performed. Finally, cell-to-cell communication analysis was carried out for key cells identified based on prognostic gene expression analysis in annotated cells. The six candidate migrasome-related genes were identified through the overlap of 5158 DEG set A, 1960 key module genes, and 146 DEG set B. Further screening led to the selection of T1MP1, CXCL8, and MGP as potential prognostic biomarkers. Immune-related analysis indicated that the high-risk group exhibited a better response to immunotherapy. Notably, the prognostic genes showed elevated expression levels in monocytes and tissue stem cells, thereby designating them as key cell types. We conducted bioinformatic analysis of migrasome-related genes and identified significant involvement of T1MP1, CXCL8, and MGP in influencing CRC prognosis and immunotherapy response. Our research provides novel insights into the role of migrasomes in CRC biology.

摘要

研究强调了迁移体作为细胞间通讯和信号传导介质的作用,这对影响肿瘤发生和进展至关重要。然而,与迁移体相关的基因及其在结直肠癌预后中的潜在作用仍未得到探索。在TCGA - CRC数据集中鉴定了差异表达基因集A(DEG集A),并进行了加权基因共表达网络分析(WGCNA)以识别与迁移体相关基因(MRG)评分相关的最重要模块。确定了单细胞RNA - seq数据集GSE231559的DEG集B。通过将DGE集A、关键模块基因和DEG集B相交来筛选候选迁移体相关基因。随后通过回归分析筛选预后基因,并建立了风险模型。根据风险评分的最佳临界值,将TCGA队列中的结直肠癌患者分为高风险和低风险组。然后进行免疫治疗反应相关分析。最后,对基于注释细胞中预后基因表达分析确定的关键细胞进行细胞间通讯分析。通过5158个DEG集A、1960个关键模块基因和146个DEG集B的重叠鉴定出六个候选迁移体相关基因。进一步筛选后选择T1MP1、CXCL8和MGP作为潜在的预后生物标志物。免疫相关分析表明高风险组对免疫治疗表现出更好的反应。值得注意的是,预后基因在单核细胞和组织干细胞中表达水平升高,因此将它们指定为关键细胞类型。我们对迁移体相关基因进行了生物信息学分析,并确定T1MP1、CXCL8和MGP在影响结直肠癌预后和免疫治疗反应方面有显著作用。我们的研究为迁移体在结直肠癌生物学中的作用提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdc5/12024535/a542db3d606b/biomedicines-13-00799-g001.jpg

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