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整合单细胞RNA测序和批量RNA测序以构建用于预测口腔鳞状细胞癌预后和免疫反应的中性粒细胞预后模型。

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.

作者信息

Wang Jinhang, Cui Zifeng, Song Qiwen, Yang Kaicheng, Chen Yanping, Peng Shixiong

机构信息

Department of Stomatology, The Second Hospital of Shijiazhuang, Shijiazhuang, Hebei, China.

Department of Stomatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.

出版信息

Hum Genomics. 2024 Dec 26;18(1):140. doi: 10.1186/s40246-024-00712-7.

Abstract

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.

摘要

背景

口腔鳞状细胞癌(OSCC)是一种侵袭性恶性肿瘤,预后较差。中性粒细胞浸润与OSCC的不良预后相关,但其潜在的分子机制仍不清楚。

方法

本研究将单细胞转录组学(scRNA-seq)与批量RNA-seq数据相结合,以分析OSCC中的中性粒细胞浸润模式,并使用加权基因共表达网络分析(hdWGCNA)确定关键基因模块。基于单变量和Lasso-Cox回归分析建立了一个预后模型,将患者分为高风险组和低风险组。进行了免疫景观和药物敏感性分析,以探索组间差异。此外,采用孟德尔随机化分析来确定与OSCC进展有因果关系的基因。

结果

确定了与OSCC进展中中性粒细胞相互作用相关的几个关键途径,从而构建了一个基于显著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。免疫景观分析显示两组之间在细胞浸润模式和TIDE评分方面存在显著差异。药物敏感性分析突出了高风险组和低风险组在药物反应性方面的差异。

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b31d/11670365/665f0238f49a/40246_2024_712_Fig1_HTML.jpg

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