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CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
食管鳞状细胞癌关键转录因子的鉴定与分析
英文原题：Identification and analysis of key transcription factors in esophageal squamous cell carcinoma.
查看英文原题
Identification and analysis of key transcription factors in esophageal squamous cell carcinoma.
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研究概要
scRNA-seq 分析揭示了核心转录因子在不同细胞簇中的表达。
中文摘要
背景与目的
过去十年，转录因子（TF）已成为多种疾病的重要参与者。免疫治疗作为有效治疗方式日益受到关注，但免疫检查点抑制剂耐药仍是挑战。TF在食管鳞状细胞癌（ESCC）免疫治疗中的调控作用尚不明确。本研究旨在探讨ESCC关键TF的表达、预测意义及其与肿瘤微环境（TME）细胞浸润的关系。
方法
表达谱来自基因表达综合数据库（GEO），TF基因数据取自TTRUST转录调控关系数据库。通过蛋白质-蛋白质相互作用（PPI）网络和富集分析阐明ESCC中的分子过程。我们在合并ESCC队列中研究TME细胞浸润图谱，并采用单样本基因集富集分析（ssGSEA）测量细胞浸润相对丰度。使用ROC分析评估核心TF对ESCC的诊断价值。
结果
研究发现正常组织与ESCC组织之间有48个差异表达TF，并发现EZH2、FOS、KLF4、FOSB、TWIST1、KLF6和CEBPB之间存在强关联。结果提示，EZH2、TWIST1和KLF4上调与免疫抑制细胞（Treg、MDSC）浸润相关，并伴随PD-1/PD-L2检查点表达降低。FOSB和CEBPB下调与NK细胞活性增强相关。ROC分析评估了这些关键TF在ESCC中的诊断潜力（EZH2，AUC=0.95；TWIST1，AUC=0.85；CEBPB，AUC=0.84；FOSB，AUC=0.79；KLF4，AUC=0.97；FOS，AUC=0.84；KLF6，AUC=0.84）。单细胞数据证实TF在肿瘤细胞、巨噬细胞和T细胞亚群中表达，提示其参与TME重塑。
结论
单细胞RNA测序分析显示核心TF在不同细胞群中的表达情况。本研究考察了与患者预后和ESCC肿瘤微环境细胞浸润相关的差异表达TF。
展开英文摘要原文
BACKGROUND AND OBJECTIVE
Over the past decade, transcription factors (TFs) have emerged as key players in various diseases. Immunotherapy has gained traction as an effective treatment, despite resistance to immune checkpoint inhibitors remains a challenge. The regulatory role of TFs in immunotherapy for esophageal squamous cell carcinoma (ESCC) is poorly understood. This study aims to explore the expression of key TFs, predictive significance, and tumor microenvironment (TME) cell infiltration in ESCC.
METHODS
The expression profiles were obtained from Gene Expression Omnibus (GEO) databases, TF gene data were obtained from the Transcriptional Regulatory Relationships Unraveled by Sentence-based Text mining (TTRUST) database. A protein-protein interaction (PPI) network and enrichment analysis elucidated the molecular processes in ESCC. We investigated the TME cell infiltration landscape in a combined ESCC cohort. The relative abundance of cell infiltration was measured using a single-sample gene-set enrichment analysis (ssGSEA). The diagnostic value of hub TFs for ESCC was investigated using ROC analysis.
RESULTS
This study found 48 differentially expressed TFs between normal and ESCC tissues and revealed a strong association between EZH2, FOS, KLF4, FOSB, TWIST1, KLF6 and CEBPB. The results suggested that upregulated EZH2, TWIST1, and KLF4 correlated with immunosuppressive cell infiltration (Tregs, MDSCs) and reduced PD-1/PD-L2 checkpoint expression. Downregulated FOSB and CEBPB associated with enhanced NK cell activity. The diagnostic potential of these key transcription factors in ESCC was evaluated through ROC analysis (EZH2, area under the curve [AUC] = 0.95; TWIST1, AUC = 0.85; CEBPB, AUC = 0.84; FOSB, AUC = 0.79; KLF4, AUC = 0.97; FOS, AUC = 0.84; KLF6, AUC = 0.84). Single-cell data confirmed TF expression in tumor cells, macrophages, and T-cell subsets, highlighting their role in TME remodeling.
CONCLUSION
The scRNA-seq analysis revealed the expression of hub TFs in different cell clusters. The study investigated the expression of DETFs associated with patient prognosis and TME cell infiltration in ESCC.
论文信息
- 作者
- Chen ZR、Cheng ZY、Zhou SW、Zhang YH、Gao Y、Yu CT、Tian B、Zhang X
- 第一作者单位
- Department of Gastroenterology, National Clinical Research Center for Digestive Diseases, Changhai Hospital, Naval Medical University, Shanghai, China.China
- 通讯作者单位
- Department of Gastroenterology, National Clinical Research Center for Digestive Diseases, Changhai Hospital, Naval Medical University, Shanghai, China. wangluoweimd@126.com.China
- 期刊
- Discover oncology2025 Oct 3
- 原文标识
- PubMed 41042414 · DOI 10.1007/s12672-025-03634-5
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