CDHu40:神经内分泌性前列腺癌的新型标记基因集。

IF 6.8 2区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS
Sheng Liu, Hye Seung Nam, Ziyu Zeng, Xuehong Deng, Elnaz Pashaei, Yong Zang, Lei Yang, Chenglong Li, Jiaoti Huang, Michael K Wendt, Xin Lu, Rong Huang, Jun Wan
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引用次数: 0

摘要

前列腺癌(PCa)是美国男性发病率最高的癌症。阉割耐药前列腺癌(CRPC)可在 PCa 接受激素治疗期间出现,表现为血清前列腺特异性抗原水平升高、疾病持续进展和/或转移到新的部位,导致预后不良。CRPC患者中有一部分表现为神经内分泌(NE)表型,表明对雄激素受体信号的依赖性降低或消失,预后特别差。在这项研究中,我们采用了基于基因表达谱和蛋白质相互作用网络的计算方法。我们确定了 500 个潜在的标记基因,这些基因在细胞周期和神经元过程中明显富集。前 40 个候选基因统称为 CDHu40,它们在根据基因表达谱区分 NE PCa(NEPC)和非 NEPC 样本方面表现出卓越的性能。CDHu40 的表现优于大多数其他已发表的标记集,尤其是在预后层面。值得注意的是,CDHu40 中的一些标记基因在其他标记集中并不存在,但有文献报道它们与 NEPC 相关,如 DDC、FOLH1、BEX1、MAST1 和 CACNA1A。重要的是,从我们的预测模型中得出的 CDHu40 得分升高与患者的不良生存结果显示出很强的相关性,这表明 CDHu40 得分有可能成为预测 NE 表型患者生存预后的指标。对顶级候选基因的动因富集分析表明,REST和E2F6可能是NEPC进展过程中的关键调控因子。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
CDHu40: a novel marker gene set of neuroendocrine prostate cancer.

Prostate cancer (PCa) is the most prevalent cancer affecting American men. Castration-resistant prostate cancer (CRPC) can emerge during hormone therapy for PCa, manifesting with elevated serum prostate-specific antigen levels, continued disease progression, and/or metastasis to the new sites, resulting in a poor prognosis. A subset of CRPC patients shows a neuroendocrine (NE) phenotype, signifying reduced or no reliance on androgen receptor signaling and a particularly unfavorable prognosis. In this study, we incorporated computational approaches based on both gene expression profiles and protein-protein interaction networks. We identified 500 potential marker genes, which are significantly enriched in cell cycle and neuronal processes. The top 40 candidates, collectively named CDHu40, demonstrated superior performance in distinguishing NE PCa (NEPC) and non-NEPC samples based on gene expression profiles. CDHu40 outperformed most of the other published marker sets, excelling particularly at the prognostic level. Notably, some marker genes in CDHu40, absent in the other marker sets, have been reported to be associated with NEPC in the literature, such as DDC, FOLH1, BEX1, MAST1, and CACNA1A. Importantly, elevated CDHu40 scores derived from our predictive model showed a robust correlation with unfavorable survival outcomes in patients, indicating the potential of the CDHu40 score as a promising indicator for predicting the survival prognosis of those patients with the NE phenotype. Motif enrichment analysis on the top candidates suggests that REST and E2F6 may serve as key regulators in the NEPC progression.

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来源期刊
Briefings in bioinformatics
Briefings in bioinformatics 生物-生化研究方法
CiteScore
13.20
自引率
13.70%
发文量
549
审稿时长
6 months
期刊介绍: Briefings in Bioinformatics is an international journal serving as a platform for researchers and educators in the life sciences. It also appeals to mathematicians, statisticians, and computer scientists applying their expertise to biological challenges. The journal focuses on reviews tailored for users of databases and analytical tools in contemporary genetics, molecular and systems biology. It stands out by offering practical assistance and guidance to non-specialists in computerized methodologies. Covering a wide range from introductory concepts to specific protocols and analyses, the papers address bacterial, plant, fungal, animal, and human data. The journal's detailed subject areas include genetic studies of phenotypes and genotypes, mapping, DNA sequencing, expression profiling, gene expression studies, microarrays, alignment methods, protein profiles and HMMs, lipids, metabolic and signaling pathways, structure determination and function prediction, phylogenetic studies, and education and training.
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