Prognosis of cholangiocarcinoma patients based on multiple patterns of programmed cell death, integrated analysis of the immune microenvironment and drug sensitivity.

IF 2.8 3区生物学 Q2 GENETICS & HEREDITY

Frontiers in Genetics Pub Date : 2025-05-14 eCollection Date: 2025-01-01 DOI:10.3389/fgene.2025.1457204

Yupeng Xu, Jian Sun, Xin Yan, Zhenliao Mao, Yiming Chen

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引用次数: 0

Abstract

Background: Cholangiocarcinoma (CHOL) is a highly malignant bile duct cancer with a poor prognosis and rising incidence. Programmed cell death (PCD) plays a crucial role in cancer biology, influencing tumor immunity and treatment response. This study analyzes the impact of multiple PCD patterns on CHOL prognosis, tumor microenvironment (TME) and drug sensitivity.

Methods: RNA sequencing data from TCGA-CHOL and GSE107943 were analyzed to identify PCD-related genes. A PCD-associated Risk Score was constructed using Cox and Lasso regression analyses. The score's prognostic value was assessed through survival analysis, ROC curves, and functional annotation.

Results: We identified 111 differentially expressed PCD-related genes, including NCK2, BNIP3 and BIK, that constituted PCD-associated Risk Score and correlated with prognosis of CHOL. Functional analyses indicated enrichment in immune-related processes. High-risk patients showed increased immune cell infiltration and higher immune checkpoint expression, suggesting a benefit from immunotherapy. They also demonstrated greater sensitivity to several chemotherapeutic and targeted agents.

Conclusion: PCD-associated Risk Score is a robust prognostic tool for CHOL, influencing TME modulation and therapeutic response, and may guide personalized treatment strategies.

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基于细胞程序性死亡多模式、免疫微环境及药物敏感性综合分析的胆管癌患者预后

背景：胆管癌（cholangicarcinoma， CHOL）是一种预后差且发病率上升的高度恶性胆管癌。程序性细胞死亡（PCD）在肿瘤生物学中起着至关重要的作用，影响肿瘤免疫和治疗反应。本研究分析多种PCD模式对CHOL预后、肿瘤微环境（tumor microenvironment， TME）及药物敏感性的影响。方法：分析TCGA-CHOL和GSE107943的RNA测序数据，鉴定pcd相关基因。采用Cox和Lasso回归分析构建pcd相关风险评分。通过生存分析、ROC曲线和功能标注评估评分的预后价值。结果：我们鉴定出111个差异表达的pcd相关基因，包括NCK2、BNIP3和BIK，这些基因构成了pcd相关风险评分，并与CHOL的预后相关。功能分析表明在免疫相关过程中富集。高危患者免疫细胞浸润增加，免疫检查点表达增高，提示免疫治疗有益。它们对几种化疗药物和靶向药物也表现出更大的敏感性。结论：pcd相关风险评分是CHOL的可靠预后工具，可影响TME调节和治疗反应，并可指导个性化治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Genetics Biochemistry, Genetics and Molecular Biology-Molecular Medicine

CiteScore

5.50

自引率

8.10%

发文量

3491

审稿时长

14 weeks

期刊介绍： Frontiers in Genetics publishes rigorously peer-reviewed research on genes and genomes relating to all the domains of life, from humans to plants to livestock and other model organisms. Led by an outstanding Editorial Board of the world’s leading experts, this multidisciplinary, open-access journal is at the forefront of communicating cutting-edge research to researchers, academics, clinicians, policy makers and the public. The study of inheritance and the impact of the genome on various biological processes is well documented. However, the majority of discoveries are still to come. A new era is seeing major developments in the function and variability of the genome, the use of genetic and genomic tools and the analysis of the genetic basis of various biological phenomena.