胃癌中偏头痛相关预后基因:转录组学和免疫治疗分析。

IF 2.8 4区 医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
OncoTargets and therapy Pub Date : 2025-08-13 eCollection Date: 2025-01-01 DOI:10.2147/OTT.S528050
Wei Qiu, Ke Zhang, Wei Hu, DongSheng Liu
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引用次数: 0

摘要

导论:胃癌(GC)是世界范围内癌症相关死亡的主要原因之一,其发病机制复杂,预后差。偏头痛小体作为一种新发现的细胞器,在肿瘤微环境调节和免疫调节中发挥着重要作用。然而,它们在GC中的具体机制在很大程度上仍然未知。方法:本研究将来自Cancer Genome Atlas (TCGA)和Gene Expression Omnibus (GEO)数据库的GC转录组学数据与35个migrasome-related genes (MRGs)相结合,通过生物信息学分析鉴定差异表达基因。采用最小绝对收缩和选择算子(LASSO)和Cox回归构建预后模型,并通过基因集富集分析(GSEA)、免疫浸润评估和药物敏感性评估进行后续分析。通过逆转录定量聚合酶链反应(RT-qPCR)在临床样品中进一步验证关键基因的表达。结果:共鉴定出8个与偏头痛相关的预后基因(BMP1、CPQ、PDGFD、TSPAN5、TSPAN7、TGFB2、WNT11和LEFTY1)。开发的风险评分模型在训练组和验证组均显示出预测性能(曲线下面积(AUC) 0.6)。功能分析显示,这些基因在关键通路,特别是TGF-β信号通路中显著富集。免疫谱分析显示高危人群的微环境特征明显,对特定化疗药物(如BMS-754807)的敏感性也存在差异。实验验证证实GC组织中BMP1 (p < 0.05)、LEFTY1 (p < 0.05)和TGFB2 (p < 0.01)显著上调,TSPAN5下调(p < 0.001)。结论:本研究揭示了8个与胃癌迁移有关的基因的预后价值。建立的风险模型为个性化GC治疗提供了新的分子标记和潜在的治疗靶点。这些发现为理解GC的发病机制和开发创新的治疗策略提供了重要的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Migrasome-Related Prognostic Genes in Gastric Cancer: A Transcriptomic and Immunotherapeutic Analysis.

Introduction: Gastric cancer (GC) remains one of the leading causes of cancer-related deaths worldwide, characterized by complex pathogenesis and poor prognosis. Migrasomes, as newly discovered organelles, play crucial roles in tumor microenvironment modulation and immune regulation. However, their specific mechanisms in GC remain largely unknown.

Methods: This study integrated GC transcriptomic data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases with 35 migrasome-related genes (MRGs) to identify differentially expressed genes through bioinformatics analysis. A prognostic model was constructed using least absolute shrinkage and selection operator (LASSO) and Cox regression, and subsequent analyses were conducted through gene set enrichment analysis (GSEA), immune infiltration assessment, and drug sensitivity evaluation. Key gene expressions were further verified in clinical samples via reverse transcription quantitative polymerase chain reaction (RT-qPCR).

Results: Eight migrasome-related prognostic genes were identified (BMP1, CPQ, PDGFD, TSPAN5, TSPAN7, TGFB2, WNT11, and LEFTY1). The developed risk-scoring model demonstrated predictive performance in both training and validation cohorts (area under the curve (AUC) > 0.6). Functional analysis revealed significant enrichment of these genes in key pathways, particularly the TGF-β signaling pathway. Immune profiling showed distinct microenvironment features in high-risk groups, along with differential sensitivity to specific chemotherapeutic agents (eg, BMS-754807). Experimental validation confirmed significant upregulation of BMP1 (p < 0.05), LEFTY1 (p < 0.05), and TGFB2 (p < 0.01), along with downregulation of TSPAN5 in GC tissues (p < 0.001).

Conclusion: This study reveals the prognostic value of eight genes related to migrators in GC. The established risk model provides novel molecular markers and potential therapeutic targets for personalized GC treatment. These findings offer critical insights for understanding GC pathogenesis and developing innovative treatment strategies.

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来源期刊
OncoTargets and therapy
OncoTargets and therapy BIOTECHNOLOGY & APPLIED MICROBIOLOGY-ONCOLOGY
CiteScore
9.70
自引率
0.00%
发文量
221
审稿时长
1 months
期刊介绍: OncoTargets and Therapy is an international, peer-reviewed journal focusing on molecular aspects of cancer research, that is, the molecular diagnosis of and targeted molecular or precision therapy for all types of cancer. The journal is characterized by the rapid reporting of high-quality original research, basic science, reviews and evaluations, expert opinion and commentary that shed novel insight on a cancer or cancer subtype. Specific topics covered by the journal include: -Novel therapeutic targets and innovative agents -Novel therapeutic regimens for improved benefit and/or decreased side effects -Early stage clinical trials Further considerations when submitting to OncoTargets and Therapy: -Studies containing in vivo animal model data will be considered favorably. -Tissue microarray analyses will not be considered except in cases where they are supported by comprehensive biological studies involving multiple cell lines. -Biomarker association studies will be considered only when validated by comprehensive in vitro data and analysis of human tissue samples. -Studies utilizing publicly available data (e.g. GWAS/TCGA/GEO etc.) should add to the body of knowledge about a specific disease or relevant phenotype and must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Bioinformatics studies must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Single nucleotide polymorphism (SNP) studies will not be considered.
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