A novel necroptosis-related genes signature to predict prognosis and treatment response in bladder cancer.

IF 3.9 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Frontiers in Molecular Biosciences Pub Date : 2024-11-25 eCollection Date: 2024-01-01 DOI:10.3389/fmolb.2024.1493411

Dongnuan Yao, Weitao Yu, Xueming Ma, Junqiang Tian

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Abstract

Background: Necroptosis, a form of programmed inflammatory cell death, plays a crucial role in tumor development, necrosis, metastasis, and immune response. This study aimed to explore the role of necroptosis in BLCA and construct a new prognostic model to guide clinical treatment and predict individualized treatment response.

Methods: The transcriptome profiling and the corresponding clinical data of BLCA patients were obtained from the Cancer Genome Atlas database (TCGA) and GEO databases. Univariate, multivariate and LASSO Cox regression analyses were used to identify and construct prognostic features associated with necroptosis. We constructed and validated a prognostic model associated with the patient's overall survival (OS). A nomogram was established to predict the survival rates of BLCA patients. Finally, the correlation between risk scores and tumor immune microenvironment, somatic mutations, immunotherapy, and chemotherapy was comprehensively analyzed.

Results: The study found two distinct NRG clusters and three gene subtypes, with significant differences in pathway enrichment and immune cell infiltration associated with different NRG clusters in the TME. In addition, we screened out six necroptosis prognosis-related genes (including PPP2R3A; CERCAM; PIK3IP1; CNTN1; CES1 and CD96) to construct a risk score prognostic model. Significant differences in overall survival rate, immune cell infiltration status, and somatic mutations existed between the high and low-risk scores in BLCA patients. Finally, drug sensitivity analysis showed that high-risk patients benefited more from immunotherapy and chemotherapy drugs.

Conclusion: This study explores the importance of necroptosis in the prognosis of patients with BLCA, and the prognostic features associated with necroptosis that we identified can serve as new biomarkers to help develop more precise treatment strategies.

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一种预测膀胱癌预后和治疗反应的新坏死相关基因标记。

背景：坏死性上睑塌陷是程序性炎症细胞死亡的一种形式，在肿瘤的发展、坏死、转移和免疫反应中起着至关重要的作用。本研究旨在探讨坏死性上睑下垂在BLCA中的作用，并构建新的预后模型来指导临床治疗和预测个体化治疗反应。方法：从癌症基因组图谱数据库（Cancer Genome Atlas database， TCGA）和GEO数据库中获取BLCA患者的转录组分析和相应的临床资料。采用单因素、多因素和LASSO Cox回归分析来确定和构建与坏死性上睑下垂相关的预后特征。我们构建并验证了与患者总生存期（OS）相关的预后模型。建立了预测BLCA患者生存率的nomogram。最后，综合分析风险评分与肿瘤免疫微环境、体细胞突变、免疫治疗、化疗的相关性。结果：研究发现两种不同的NRG簇和三种基因亚型，不同NRG簇在TME中的通路富集和免疫细胞浸润存在显著差异。此外，我们筛选了6个坏死性上睑下垂预后相关基因(包括PPP2R3A；CERCAM;PIK3IP1;CNTN1;CES1和CD96)构建风险评分预后模型。BLCA患者的总生存率、免疫细胞浸润状态和体细胞突变在高危评分与低危评分之间存在显著差异。最后，药物敏感性分析显示，高危患者更受益于免疫治疗和化疗药物。结论：本研究探讨了坏死性上睑下垂对BLCA患者预后的重要性，我们发现的与坏死性上睑下垂相关的预后特征可以作为新的生物标志物，帮助制定更精确的治疗策略。

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 Molecular Biosciences Biochemistry, Genetics and Molecular Biology-Biochemistry

CiteScore

7.20

自引率

4.00%

发文量

1361

审稿时长

14 weeks

期刊介绍： Much of contemporary investigation in the life sciences is devoted to the molecular-scale understanding of the relationships between genes and the environment — in particular, dynamic alterations in the levels, modifications, and interactions of cellular effectors, including proteins. Frontiers in Molecular Biosciences offers an international publication platform for basic as well as applied research; we encourage contributions spanning both established and emerging areas of biology. To this end, the journal draws from empirical disciplines such as structural biology, enzymology, biochemistry, and biophysics, capitalizing as well on the technological advancements that have enabled metabolomics and proteomics measurements in massively parallel throughput, and the development of robust and innovative computational biology strategies. We also recognize influences from medicine and technology, welcoming studies in molecular genetics, molecular diagnostics and therapeutics, and nanotechnology. Our ultimate objective is the comprehensive illustration of the molecular mechanisms regulating proteins, nucleic acids, carbohydrates, lipids, and small metabolites in organisms across all branches of life. In addition to interesting new findings, techniques, and applications, Frontiers in Molecular Biosciences will consider new testable hypotheses to inspire different perspectives and stimulate scientific dialogue. The integration of in silico, in vitro, and in vivo approaches will benefit endeavors across all domains of the life sciences.