整合单细胞 RNA-Seq 和批量 RNA-Seq 构建新型人乳头瘤病毒感染宫颈癌 γδT 细胞相关预后标志物。
Integrating Single-Cell RNA-Seq and Bulk RNA-Seq to Construct a Novel γδT Cell-Related Prognostic Signature for Human Papillomavirus-Infected Cervical Cancer.
机构信息
Department of Dermatology, The First People's Hospital of Yunnan Province, the Affiliated Hospital of Kunming University of Science and Technology, Yunnan Provincial Key Laboratory of Clinical Virology, Kunming, China.
出版信息
Cancer Control. 2024 Jan-Dec;31:10732748241274228. doi: 10.1177/10732748241274228.
BACKGROUND
Gamma delta (γδ) T cells play dual roles in human tumors, with both antitumor and tumor-promoting functions. However, the role of γδT cells in HPV-infected cervical cancer is still undetermined. Therefore, we aimed to identify γδT cell-related prognostic signatures in the cervical tumor microenvironment.
METHODS
Single-cell RNA-sequencing (scRNA-seq) data, bulk RNA-seq data, and corresponding clinical information of cervical cancer patients were obtained from the TCGA and GEO databases. The Seurat R package was used for single-cell analysis, and machine learning algorithms were used to screen and construct a γδT cell-related prognostic signature. Real-time quantitative PCR (RT-qPCR) was performed to detect the expression of prognostic signature genes.
RESULTS
Single-cell analysis indicated distinct populations of γδT cells between HPV-positive (HPV+) and HPV-negative (HPV-) cervical cancers. A trajectory analysis indicated γδT cells clustered into differential clusters with the pseudotime. High-dimensional Weighted Gene Co-expression Network Analysis (hdWGCNA) identified the key γδT cell-related gene modules. Bulk RNA-seq analysis also demonstrated the heterogeneity of immune cells, and the γδT-score was positively associated with inflammatory response and negatively associated with MYC stemness. Eight γδT cell-related hub genes (GTRGs), including ITGAE, IKZF3, LSP1, NEDD9, CLEC2D, RBPJ, TRBC2, and OXNAD1, were selected and validated as a prognostic signature for cervical cancer.
CONCLUSION
We identified γδT cell-related prognostic signatures that can be considered independent factors for survival prediction in cervical cancer.
背景
γδT 细胞在人类肿瘤中发挥双重作用，具有抗肿瘤和促进肿瘤的功能。然而，γδT 细胞在 HPV 感染的宫颈癌中的作用仍不确定。因此，我们旨在确定宫颈肿瘤微环境中与 γδT 细胞相关的预后特征。
方法
从 TCGA 和 GEO 数据库中获取宫颈癌患者的单细胞 RNA 测序（scRNA-seq）数据、批量 RNA-seq 数据和相应的临床信息。使用 Seurat R 包进行单细胞分析，并使用机器学习算法筛选和构建与 γδT 细胞相关的预后特征。实时定量 PCR（RT-qPCR）检测预后特征基因的表达。
结果
单细胞分析表明 HPV 阳性（HPV+）和 HPV 阴性（HPV-）宫颈癌之间存在不同的 γδT 细胞群体。轨迹分析表明，γδT 细胞在伪时间上聚集到不同的簇中。高维加权基因共表达网络分析（hdWGCNA）鉴定出关键的 γδT 细胞相关基因模块。批量 RNA-seq 分析也显示了免疫细胞的异质性，γδT 评分与炎症反应呈正相关，与 MYC 干性呈负相关。选择和验证了 8 个与 γδT 细胞相关的枢纽基因（GTRGs），包括 ITGAE、IKZF3、LSP1、NEDD9、CLEC2D、RBPJ、TRBC2 和 OXNAD1，作为宫颈癌的预后特征。
结论
我们鉴定了与 γδT 细胞相关的预后特征，这些特征可被视为宫颈癌生存预测的独立因素。
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