PAQR4:影响膀胱尿路上皮癌免疫逃避和转移的关键衰老相关基因

IF 3.7 2区 医学 Q2 GENETICS & HEREDITY
Yizhang Sun, Xincheng Yi, Chenchao Zhou, Yuhua Huang
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引用次数: 0

摘要

背景:膀胱尿路上皮癌(BLCA)是一种常见的恶性肿瘤,以其高复发率和有限的治疗效果而闻名。细胞衰老已被广泛证明通过细胞周期阻滞抑制肿瘤发生。因此,识别衰老相关的生物标志物对于提高BLCA的诊断、预后和免疫治疗结果至关重要。方法:本研究整合TCGA-BLCA和GSE13507数据集,对衰老相关基因进行分析。聚类分析采用ConsensusClusterPlus,免疫浸润评估采用CIBERSORT。通过结合各种机器学习算法,开发并验证了BLCA的诊断和预后模型。通过qRT-PCR、菌落形成和Transwell实验验证PAQR4的功能作用。结果:我们的研究显示,与衰老相关的样本显示出更高的生存率和更低的高级别肿瘤发生率。聚类分析确定了两个不同的BLCA亚群,其特征是独特的免疫浸润谱和对免疫检查点封锁的不同反应。根据衰老相关基因建立的诊断和预后模型随后得到验证。值得注意的是,PAQR4被确定为与不良预后和免疫抑制微环境相关的关键衰老相关基因。PAQR4基因的下调可显著抑制BLCA细胞的增殖和转移。结论:PAQR4是一种新的生物标志物和治疗靶点,影响细胞衰老、免疫逃避和转移。该研究为BLCA的衰老相关机制提供了新的见解,并为BLCA的精确诊断和免疫治疗的优化提供了工具。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

PAQR4: A Critical Senescence-Related Gene Influencing Immune Evasion and Metastasis in Bladder Urothelial Carcinoma

PAQR4: A Critical Senescence-Related Gene Influencing Immune Evasion and Metastasis in Bladder Urothelial Carcinoma

Background: Bladder urothelial carcinoma (BLCA) is a prevalent malignant tumor known for its high recurrence rates and limited therapeutic efficacy. Cellular senescence has been extensively shown to inhibit tumorigenesis via cell cycle arrest. Consequently, the identification of senescence-associated biomarkers is essential for enhancing the diagnosis, prognosis, and immunotherapeutic outcomes of BLCA.

Method: This study integrated the TCGA-BLCA and GSE13507 datasets to analyze senescence-related genes. ConsensusClusterPlus was employed for cluster analysis, while immune infiltration was assessed using CIBERSORT. A diagnostic and prognostic model for BLCA was developed and validated through the combination of various machine learning algorithms. Experimental validation was conducted using qRT-PCR, colony formation, and Transwell assays to evaluate the functional role of PAQR4.

Result: Our study revealed that aging-related samples demonstrated improved survival rates and a lower incidence of high-grade tumors. Cluster analysis identified two distinct subgroups of BLCA characterized by unique immune infiltration profiles and varying responses to immune checkpoint blockade. The diagnostic and prognostic models developed from aging-related genes were subsequently validated. Notably, PAQR4 was identified as a critical aging-related gene linked to poor prognosis and an immunosuppressive microenvironment. The knockdown of PAQR4 significantly inhibited the proliferation and metastasis of BLCA cells.

Conclusion: PAQR4 is a novel biomarker and therapeutic target for BLCA, influencing cellular senescence, immune evasion, and metastasis. This study provides insights into the senescence-related mechanisms and offers tools for precision diagnosis and the optimization of immunotherapy in BLCA.

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来源期刊
Human Mutation
Human Mutation 医学-遗传学
CiteScore
8.40
自引率
5.10%
发文量
190
审稿时长
2 months
期刊介绍: Human Mutation is a peer-reviewed journal that offers publication of original Research Articles, Methods, Mutation Updates, Reviews, Database Articles, Rapid Communications, and Letters on broad aspects of mutation research in humans. Reports of novel DNA variations and their phenotypic consequences, reports of SNPs demonstrated as valuable for genomic analysis, descriptions of new molecular detection methods, and novel approaches to clinical diagnosis are welcomed. Novel reports of gene organization at the genomic level, reported in the context of mutation investigation, may be considered. The journal provides a unique forum for the exchange of ideas, methods, and applications of interest to molecular, human, and medical geneticists in academic, industrial, and clinical research settings worldwide.
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