纵向血浆代谢组学指导食管鳞状细胞癌化疗免疫治疗的动态风险评估与饮食调节
Longitudinal Plasma Metabolomics Guides Dynamic Risk Assessment and Dietary Modulation for Esophageal Squamous Cell Cancer Chemoimmunotherapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
鉴定食管鳞状细胞癌中 2 种与泛素-蛋白酶体系统相关的亚型用于预后和免疫治疗反应预测
英文原题：Identification of 2 Ubiquitin-Proteasome System-Related Subtypes in Esophageal Squamous Cell Carcinoma for Prognostic and Immunotherapeutic Response Prediction.
查看英文原题
Identification of 2 Ubiquitin-Proteasome System-Related Subtypes in Esophageal Squamous Cell Carcinoma for Prognostic and Immunotherapeutic Response Prediction.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
中文摘要
泛素-蛋白酶体系统（UPS）参与食管鳞状细胞癌（ESCC）的发病和进展，是一个有前景的治疗靶点。然而，UPS在ESCC中的临床意义仍未完全阐明。首先通过单因素Cox回归分析筛选与ESCC生存相关的UPS基因。基于这些基因对TCGA-ESCC队列进行共识聚类。对不同聚类进行功能富集、肿瘤免疫微环境分析，并进行体细胞突变分析。评估潜在的治疗靶点和生物标志物，并构建miRNA-TF-hub基因调控网络。ESCC样本被分为2个不同的聚类（聚类1和聚类2），其中聚类1表现出更优的总生存期。差异分析揭示细胞黏附和钙信号通路的富集。免疫浸润分析表明聚类2中CD8+ T细胞、肥大细胞、中性粒细胞和TILs升高，同时TIDE评分较低。TP53表现出最高的突变频率（聚类1 vs. 聚类2为93% vs. 86%）。Selumetinib、entinostat和erlotinib被确定为聚类2的候选药物，而tozasertib、alpelisib和cediranib对聚类1表现出更高的适用性。表征了10个潜在生物标志物、13个转录因子和2个miRNA。
本研究阐明了UPS在ESCC进展中的作用，并为个性化治疗策略提供了框架。
展开英文摘要原文
Ubiquitin-proteasome system (UPS) is implicated in pathogenesis and progression of esophageal squamous cell carcinoma (ESCC), representing a promising therapeutic target.
However, clinical significance of UPS in ESCC remains incompletely elucidated. UPS genes associated with ESCC survival were first screened through univariate Cox regression analysis. Consensus clustering was performed on TCGA-ESCC cohort based on these genes. Functional enrichment, tumor immune microenvironment analysis, and somatic mutation profiling were conducted for different clusters. Potential therapeutics and biomarkers were evaluated, and miRNA-TF-hub gene regulatory network was constructed. ESCC samples were stratified into 2 distinct clusters (cluster 1 and cluster 2), with cluster 1 demonstrating superior overall survival.
Differential analysis revealed enrichment in cell adhesion and calcium signaling pathways. Immune infiltration analysis indicated elevated CD8+ T cells, mast cells, neutrophils, and TILs in cluster 2, alongside lower TIDE scores. TP53 exhibited the highest mutation frequency (93% vs.
86% in cluster 1 vs. cluster 2). Selumetinib, entinostat, and erlotinib were identified as candidate drugs for cluster 2, whereas tozasertib, alpelisib, and cediranib showed higher suitability for cluster 1. Ten potential biomarkers, 13 transcription factors, and 2 miRNAs were characterized.
This study elucidates the role of UPS in ESCC progression and provides a framework for personalized treatment strategies.
论文信息
- 作者
- Jiang C、Shen M、Zhu J、Zhang X、Chen K
- 单位
- Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou.China
- 期刊
- Journal of immunotherapy (Hagerstown, Md. : 1997)2026 Jun 1
- 原文标识
- PubMed 41361165 · DOI 10.1097/CJI.0000000000000587