An Angiogenesis-Related Scoring System Identifies an Immune-Inflamed Phenotype and Characterizes the Tumor Immune Microenvironment in Esophageal Squamous Cell Carcinoma

IF 2 4区医学 Q2 MEDICINE, GENERAL & INTERNAL

International Journal of Clinical Practice Pub Date : 2026-09-28 DOI:10.1155/ijcp/1390370

Yusheng Li, Lei Xu, Chuntong Yin, Fan Wang

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引用次数: 0

Abstract

Background

Tumor angiogenesis intricately modulates the tumor immune microenvironment (TIME), but whether angiogenesis-related transcriptional features can stratify prognosis and immune phenotypes in esophageal squamous cell carcinoma (ESCC) remains unclear.

Methods

Transcriptomic and clinical data were obtained from public databases. An angiogenesis-related scoring system (ARSys) was constructed using univariate Cox regression and least absolute shrinkage and selection operator (LASSO) and then validated in an independent cohort. Prognostic performance was assessed via Cox regression and receiver operating characteristic (ROC) analysis. TIME characterization employed TIMER, ssGSEA, and ESTIMATE; pathway analyses used gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO). Key genes were screened by LASSO and support vector machine-recursive feature elimination (SVM-RFE). TNFSF10 expression was further validated by immunohistochemistry, Western blot, and RT-qPCR in clinical samples.

Results

ARSys independently predicted prognosis and stratified patients into two distinct immunophenotypes. The high-risk subgroup exhibited a markedly “immune-inflamed” phenotype, characterized by elevated infiltration of effector T cells, heightened expression of multiple immune checkpoints, and significant enrichment of inflammatory pathways (complement cascade, antigen processing, and T-cell receptor signaling). TNFSF10, a key ARSys gene with the highest weighting, was significantly upregulated in ESCC tissues at the protein and mRNA levels. This immuno-inflammatory signature indicates that ARSys^high tumors display an immune-inflamed phenotype; however, the present datasets do not permit inference regarding ICI response or irAE risk.

Conclusions

ARSys provides prognostic stratification and characterization of tumor immunophenotypes in ESCC. TNFSF10 emerges as a promising biomarker associated with unfavorable prognosis in ESCC. The potential relevance of ARSys to immunotherapy response or toxicity requires validation in dedicated ICI-treated cohorts.

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血管生成相关评分系统识别免疫炎症表型并表征食管鳞状细胞癌的肿瘤免疫微环境

肿瘤血管生成复杂地调节肿瘤免疫微环境（TIME），但血管生成相关的转录特征是否可以分层食管鳞状细胞癌（ESCC）的预后和免疫表型尚不清楚。方法从公共数据库中获取转录组学和临床资料。使用单变量Cox回归和最小绝对收缩和选择算子（LASSO）构建血管生成相关评分系统（ARSys），然后在独立队列中进行验证。通过Cox回归和受试者工作特征（ROC）分析评估预后。时间表征采用TIMER、ssGSEA和ESTIMATE；途径分析使用基因集变异分析（GSVA）、基因集富集分析（GSEA）、京都基因与基因组百科全书（KEGG）和基因本体（GO）。通过LASSO和支持向量机递归特征消除（SVM-RFE）筛选关键基因。通过免疫组织化学、Western blot和RT-qPCR进一步验证临床样本中TNFSF10的表达。结果ARSys独立预测预后，并将患者分为两种不同的免疫表型。高危亚组表现出明显的“免疫炎症”表型，其特征是效应T细胞浸润升高，多个免疫检查点表达升高，炎症途径（补体级联、抗原加工和T细胞受体信号传导）显著富集。TNFSF10是ARSys中权重最高的关键基因，在ESCC组织中蛋白和mRNA水平均显著上调。这种免疫炎症特征表明ARSyshigh肿瘤表现出免疫炎症表型；然而，目前的数据集不允许对ICI反应或irAE风险进行推断。结论ARSys提供了ESCC的预后分层和肿瘤免疫表型表征。TNFSF10作为一种与ESCC不良预后相关的有希望的生物标志物出现。ARSys与免疫治疗反应或毒性的潜在相关性需要在专门的ici治疗队列中进行验证。

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来源期刊

International Journal of Clinical Practice 医学-医学：内科

CiteScore

5.30

自引率

0.00%

发文量

274

审稿时长

3-8 weeks

期刊介绍： IJCP is a general medical journal. IJCP gives special priority to work that has international appeal. IJCP publishes: Editorials. IJCP Editorials are commissioned. [Peer reviewed at the editor''s discretion] Perspectives. Most IJCP Perspectives are commissioned. Example. [Peer reviewed at the editor''s discretion] Study design and interpretation. Example. [Always peer reviewed] Original data from clinical investigations. In particular: Primary research papers from RCTs, observational studies, epidemiological studies; pre-specified sub-analyses; pooled analyses. [Always peer reviewed] Meta-analyses. [Always peer reviewed] Systematic reviews. From October 2009, special priority will be given to systematic reviews. [Always peer reviewed] Non-systematic/narrative reviews. From October 2009, reviews that are not systematic will be considered only if they include a discrete Methods section that must explicitly describe the authors'' approach. Special priority will, however, be given to systematic reviews. [Always peer reviewed] ''How to…'' papers. Example. [Always peer reviewed] Consensus statements. [Always peer reviewed] Short reports. [Always peer reviewed] Letters. [Peer reviewed at the editor''s discretion] International scope IJCP publishes work from investigators globally. Around 30% of IJCP articles list an author from the UK. Around 30% of IJCP articles list an author from the USA or Canada. Around 45% of IJCP articles list an author from a European country that is not the UK. Around 15% of articles published in IJCP list an author from a country in the Asia-Pacific region.