使用ScRNA-seq和bulk-RNA分析HPV阴性口腔鳞状细胞癌T细胞的异质性分析和预后模型构建。

IF 3.9 4区 生物学 Q1 GENETICS & HEREDITY
Chunyan Li, Zengbo Lv, Chongxin Li, Shixuan Yang, Feineng Liu, Tengfei Zhang, Lin Wang, Wen Zhang, Ruoyu Deng, Guoyu Xu, Huan Luo, Yinhong Zhao, Jialing Lv, Chao Zhang
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引用次数: 0

摘要

背景:T细胞参与肿瘤发展的各个阶段,并显著影响肿瘤微环境(tumor microenvironment, TME)。我们的目的是评估t细胞标记基因表达谱,利用这些基因建立人类乳头状瘤病毒(HPV)阴性口腔鳞状细胞癌(OSCC)的预测风险模型,并检查风险评分与免疫治疗反应之间的相关性。方法:我们从GEO数据集中获取hpv阴性OSCC的scRNA-seq数据。我们进行了t细胞相关基因的细胞间通讯、轨迹和途径富集分析。此外,我们利用TCGA和GEO数据构建并验证了hpv阴性OSCC患者的t细胞相关基因预后模型,评估了hpv阴性OSCC患者的免疫浸润状况,并采用qrt - pcr检测了不同危险人群中预后相关基因的表达水平。结果:对14例hpv阴性OSCC样本和6例正常样本的28000个细胞进行了scrna测序。我们从这些细胞中鉴定出4635个T细胞,并鉴定出774个与5种不同T细胞亚型的T细胞相关的差异表达基因(DEGs)。通过整合bulk-RNAseq数据,我们建立了基于与T细胞相关的DEGs的预后模型。根据这些预后相关基因将患者分为高危组和低危组,我们可以准确预测患者的生存率和TME的免疫浸润情况。qRT-PCR结果显示,与低危组患者相比,高危组PMEPA1、SH2D2A、SMS、PRDX4的表达均显著上调。结论:本研究为了解hpv阴性OSCC患者T细胞的异质性和相关的预后风险模型提供了资源。为预测hpv阴性OSCC患者的生存和免疫浸润水平提供了新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Heterogeneity analysis and prognostic model construction of HPV negative oral squamous cell carcinoma T cells using ScRNA-seq and bulk-RNA analysis

Background

T cells are involved in every stage of tumor development and significantly influence the tumor microenvironment (TME). Our objective was to assess T-cell marker gene expression profiles, develop a predictive risk model for human papilloma virus (HPV)-negative oral squamous cell carcinoma (OSCC) utilizing these genes, and examine the correlation between the risk score and the immunotherapy response.

Methods

We acquired scRNA-seq data for HPV-negative OSCC from the GEO datasets. We performed cell‒cell communication, trajectory, and pathway enrichment analyses of T-cell-associated genes. In addition, we constructed and validated a T-cell-associated gene prognostic model for HPV-negative OSCC patients using TCGA and GEO data and assessed the immune infiltration status of HPV-negative OSCC patients .qRT-PCR was used to detect the expression level of prognosis-related genes in different risk groups.

Results

ScRNA-seq was conducted on 28,000 cells derived from 14 HPV-negative OSCC samples and 6 normal samples. We identified 4,635 T cells from these cells and identified 774 differentially expressed genes(DEGs) associated with T cells across five distinct T-cell subtypes. Through the integration of bulk-RNAseq data, we established a prognostic model based on DEGs related to T cells. By separating patients into high-risk and low-risk groups according to these prognostic related genes, we can accurately predict their survival rates and the immune infiltration status of the TME.qRT-PCR results showed that compared with the patients of low risk group, the expression of PMEPA1, SH2D2A, SMS and PRDX4 were significantly up-regulated in high risk group.

Conclusion

This study provides a resource for understanding the heterogeneity of T cells in HPV-negative OSCC patients and associated prognostic risk models. It provides new insights for predicting survival and level of immune infiltration in patients with HPV-negative OSCC.

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来源期刊
CiteScore
3.50
自引率
3.40%
发文量
92
审稿时长
2 months
期刊介绍: Functional & Integrative Genomics is devoted to large-scale studies of genomes and their functions, including systems analyses of biological processes. The journal will provide the research community an integrated platform where researchers can share, review and discuss their findings on important biological questions that will ultimately enable us to answer the fundamental question: How do genomes work?
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