整合单细胞RNA-seq和整体RNA-seq构建预测口腔鳞状细胞癌预后和免疫应答的中性粒细胞预后模型。

IF 3.8 3区 医学 Q2 GENETICS & HEREDITY Human Genomics Pub Date : 2024-12-26 DOI:10.1186/s40246-024-00712-7
Jinhang Wang, Zifeng Cui, Qiwen Song, Kaicheng Yang, Yanping Chen, Shixiong Peng
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引用次数: 0

摘要

背景:口腔鳞状细胞癌(OSCC)是一种预后不良的侵袭性恶性肿瘤。中性粒细胞浸润与OSCC的不良预后有关,但其潜在的分子机制尚不清楚。方法:本研究将单细胞转录组学(scRNA-seq)与大量RNA-seq数据相结合,分析OSCC中性粒细胞浸润模式,并使用加权基因共表达网络分析(hdWGCNA)识别关键基因模块。基于单变量和Lasso-Cox回归分析建立预后模型,将患者分为高危组和低危组。通过免疫景观和药物敏感性分析来探讨各组的特异性差异。此外,采用孟德尔随机化分析来确定与OSCC进展相关的基因。结果:确定了与嗜中性粒细胞相互作用相关的几个关键途径,从而构建了基于重要模块基因的预后模型。该模型在区分高风险组和低风险组的生存率方面表现出很强的预测性能。免疫景观分析显示,各组细胞浸润模式和TIDE评分存在显著差异。药物敏感性分析强调了高危组和低危组之间药物反应性的差异。结论:本研究阐明了中性粒细胞及其相关基因模块在OSCC进展中的关键作用。该预后模型为患者分层和靶向治疗提供了新的参考。这些发现为OSCC的诊断、预后和免疫治疗提供了潜在的新靶点。
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Integrating single-cell RNA-seq and bulk RNA-seq to construct a neutrophil prognostic model for predicting prognosis and immune response in oral squamous cell carcinoma.

Background: Oral squamous cell carcinoma (OSCC) is an aggressive malignancy with poor prognosis. Neutrophil infiltration has been associated with unfavorable outcomes in OSCC, but the underlying molecular mechanisms remain unclear.

Methods: This study integrated single-cell transcriptomics (scRNA-seq) with bulk RNA-seq data to analyze neutrophil infiltration patterns in OSCC and identify key gene modules using weighted gene co-expression network analysis (hdWGCNA). A prognostic model was developed based on univariate and Lasso-Cox regression analyses, stratifying patients into high- and low-risk groups. Immune landscape and drug sensitivity analyses were conducted to explore group-specific differences. Additionally, Mendelian randomization analysis was employed to identify genes causally related to OSCC progression.

Results: Several key pathways associated with neutrophil interactions in OSCC progression were identified, leading to the construction of a prognostic model based on significant module genes. The model demonstrated strong predictive performance in distinguishing survival rates between high- and low-risk groups. Immune landscape analysis revealed significant differences in cell infiltration patterns and TIDE scores between the groups. Drug sensitivity analysis highlighted differences in drug responsiveness between high- and low-risk groups.

Conclusion: This study elucidates the critical role of neutrophils and their associated gene modules in OSCC progression. The prognostic model provides a novel reference for patient stratification and targeted therapy. These findings offer potential new targets for OSCC diagnosis, prognosis, and immunotherapy.

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来源期刊
Human Genomics
Human Genomics GENETICS & HEREDITY-
CiteScore
6.00
自引率
2.20%
发文量
55
审稿时长
11 weeks
期刊介绍: Human Genomics is a peer-reviewed, open access, online journal that focuses on the application of genomic analysis in all aspects of human health and disease, as well as genomic analysis of drug efficacy and safety, and comparative genomics. Topics covered by the journal include, but are not limited to: pharmacogenomics, genome-wide association studies, genome-wide sequencing, exome sequencing, next-generation deep-sequencing, functional genomics, epigenomics, translational genomics, expression profiling, proteomics, bioinformatics, animal models, statistical genetics, genetic epidemiology, human population genetics and comparative genomics.
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