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ZUP1 作为乳腺癌中一种新型潜在致癌驱动因子和预后生物标志物

英文原题:ZUP1 as a Novel Potential Oncogenic Driver and Prognostic Biomarker in Breast Cancer.

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ZUP1 as a Novel Potential Oncogenic Driver and Prognostic Biomarker in Breast Cancer.

PubMed 2026/09/08(内容时间) Comb Chem High Throughput Screen Q3 · IF 1.7(JCR 2025)

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研究概要

我们的研究确定 ZUP1 是乳腺癌中潜在的致癌因子和稳健的独立预后生物标志物。其参与关键细胞过程及对肿瘤免疫微环境的调节,凸显了其作为新型治疗靶点的潜力。包括免疫组化染色和 CCK8 增殖实验在内的功能实验,进一步支持了 ZUP1 的致癌作用。所建立的列线图为个性化风险评估和临床决策提供了有价值的工具。我们的发现表明,ZUP1 是一种新型多层面生物标志物,对乳腺癌个性化治疗策略具有重要意义。

研究思路结论见上方概要

乳腺癌是全球女性癌症死亡的主要原因之一。识别新的预测标志物和治疗靶点对于改善患者预后至关重要。含锌指U-rich RNA结合蛋白1(ZUP1)是一种含有锌指结构的RNA结合蛋白,在乳腺癌研究中尚未得到系统分析。

研究使用了来自癌症基因组图谱(TCGA)数据库的1,231个样本数据。比较了肿瘤组织和正常组织中的ZUP1表达。通过生存分析和回归模型评估了其预测价值。通过基因功能分析探讨了其生物学作用。采用免疫细胞分析方法研究肿瘤免疫环境,并利用药物敏感性数据库预测药物反应。还构建并验证了预测模型。

ZUP1在乳腺癌组织中的表达显著高于正常组织。ZUP1高表达与晚期肿瘤分期相关,并在单因素和多因素分析中均为不良生存预后的独立指标。功能富集显示,ZUP1与细胞周期进程、DNA复制和范可尼贫血(FA)通路密切相关。免疫浸润分析表明,ZUP1水平与静息肥大细胞和活化NK细胞的丰度呈显著负相关。此外,ZUP1高表达与对多种靶向治疗(包括Nutlin-3a和PD-0325901)的敏感性增加相关。开发了一种结合ZUP1表达与关键临床因素(年龄、分期、T、N、M)的临床适用列线图,用于预测3年和5年OS,具有良好的校准度和区分度。

展开英文摘要原文

The study used data from 1,231 samples from the Cancer Genome Atlas (TCGA) database. The ZUP1 expression in tumor tissues and normal tissues was compared. Its predictive value was assessed using survival analysis and regression models. Its biological role was explored through gene functional analysis. The immune cell analysis method was used to study the tumor immune environment, and the drug susceptibility database was used to predict drug responses. Predictive models were also built and validated.

ZUP1 expression was significantly higher in breast cancer tissues than in normal tissues. High expression of ZUP1 is related to advanced tumor stage and is an independent indicator of poor survival prognosis in univariate and multivariate analyses. Functional enrichment revealed that ZUP1 is closely linked to cell cycle progression, DNA replication, and the Fanconi anemia (FA) pathway. Immune infiltration analysis demonstrated a significant negative link between ZUP1 levels and the abundance of resting mast cells and activated NK cells. Furthermore, high ZUP1 expression was associated with increased sensitivity to several targeted therapies, including Nutlin-3a and PD-0325901. A clinically applicable nomogram combining ZUP1 expression with key clinical factors (age, stage, T, N, M) was developed to predict 3- and 5-year OS with good calibration and discrimination. DISCUSSION: Our study identifies ZUP1 as a potential oncogenic factor and a robust independent prognostic biomarker in breast cancer. Its involvement in critical cellular processes and modulation of the tumor immune microenvironment highlights its potential as a novel therapeutic target. Functional experiments, including immunohistochemical staining and CCK8 proliferation assays, further supported the oncogenic role of ZUP1. The established nomogram provides a valuable tool for personalized risk assessment and clinical decision-making.

Our findings suggest that ZUP1 is a novel multifaceted biomarker with significant implications for personalized treatment strategies in breast cancer.

论文信息

作者
Li W、Shan C、Zhang S、Zheng G
第一作者单位
The Comprehensive Breast Care Center, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China.China
通讯作者单位
State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and Department of Immunology, Fourth Military Medical University, Xi'an, 710032, China.China
期刊
Combinatorial chemistry & high throughput screening2026 Sep 8
原文标识
PubMed 42725597 · DOI 10.2174/0113862073486848260808184821