基于转录组的组蛋白去乙酰化酶基因网络分析发现 EMP1 是膀胱癌预后的潜在生物标记物

IF 2.3 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer Pub Date : 2024-11-01 DOI:10.1016/j.clgc.2024.102262

Qiong Bao , Yan Li , Yu Chen , Ji Zheng , Jiang Zhao , Ting Hu

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引用次数: 0

摘要

背景组蛋白去乙酰化酶（HDACs）的异常表达和功能与膀胱癌（BCa）的发生密切相关。我们探讨了HDAC家族基因在膀胱癌中的相关性和表达模式。我们采用共识聚类方法，根据HDAC表达谱将BCa分为亚型。通过差异分析、通路富集分析和药物反应性评估来确定HDAC亚型的特征。结果我们发现了不同的HDAC表达模式以及与免疫细胞浸润和癌症通路富集的相关性，突出了它们在BCa中的作用。共识聚类发现了2种HDAC基因亚型。与基因簇2相比，基因簇1显示出更差的生存率、更高的临床分期和更低的免疫细胞浸润。此外，通路富集分析显示，基因簇之间的肿瘤促进通路存在差异。此外，基因簇1对Rho激酶抑制剂的耐药性更高。多组学分析揭示了各基因簇之间独特的突变和 CNV 特征，表明它们具有不同的分子特征。此外，HDAC基因相关预后模型显示了强大的预测准确性，并确定EMP1是与生存率低和转移途径丰富相关的关键预后基因。结论我们的研究提供了对BCa中HDACs格局的全面见解，阐明了它们在肿瘤异质性、免疫调节、药物反应性和分子特征中的作用。EMP1 是 BCa 的潜在治疗靶点和预后标志物。

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Transcriptome-Based Network Analysis Related to Histone Deacetylase Genes and Identified EMP1 as a Potential Biomarker for Prognosis in Bladder Cancer

Background

Abnormal expression and function of histone deacetylases (HDACs) are closely associated with the development of bladder cancer (BCa). Systematic elucidation of the role of HDACs in BCa is expected to improve BCa prognosis and treatment strategies.

Methods

We explored the correlation and expression patterns of HDAC family genes in BCa. Consensus clustering was employed to categorize BCa into subtypes based on HDAC expression profiles. Differential analysis, pathway enrichment analysis, and drug responsiveness evaluation were conducted to characterize HDAC subtypes. Then, a prognostic model based on HDAC cluster related genes was constructed and validated across multiple cohorts.

Results

We identified distinct HDAC expression patterns and correlations with immune cell infiltration and enrichment of pathways in cancer, highlighting their role in BCa. Consensus clustering revealed 2 HDAC gene subtypes. Gene cluster 1 showed worse survival, higher clinical stage, and lower immune cell infiltration compared to gene cluster 2. Additionally, pathway enrichment analysis revealed differences in tumor-promoting pathways between the clusters. Moreover, gene cluster 1 exhibited higher resistance to Rho kinase inhibitor drugs. Multi-omic analysis unveiled unique mutation and CNV profiles between the clusters, indicating distinct molecular features. Furthermore, a HDAC gene-related prognostic model demonstrated robust predictive accuracy and identified EMP1 as a key prognostic gene associated with poor survival and enriched metastatic pathways.

Conclusion

Our study provides comprehensive insights into the landscape of HDACs in BCa, elucidating their roles in tumor heterogeneity, immune modulation, drug responsiveness, and molecular features. EMP1 is a potential therapeutic target and prognostic marker for BCa.

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来源期刊

Clinical genitourinary cancer 医学-泌尿学与肾脏学

CiteScore

5.20

自引率

6.20%

发文量

201

审稿时长

54 days

期刊介绍： Clinical Genitourinary Cancer is a peer-reviewed journal that publishes original articles describing various aspects of clinical and translational research in genitourinary cancers. Clinical Genitourinary Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of genitourinary cancers. The main emphasis is on recent scientific developments in all areas related to genitourinary malignancies. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.