PO.BCS01.04 · 生物信息与计算
前列腺癌等位基因特异性表达图谱揭示AR信号通路和耐药通路中反复出现的、分期特异性事件
Landscape of allele-specific expression in prostate cancer reveals recurrent, stage-specific events in AR signaling and resistance pathways
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作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
顺式调控改变在前列腺癌(PCa)中的作用尚未得到充分表征，这为发现驱动基因和治疗靶点提供了机会。为全面研究这些作用，我们鉴定了在局限性PCa和转移性去势抵抗性PCa(mCRPC)样本中发生等位基因特异性表达(ASE)的基因。通过界定前列腺组织中反复出现的ASE事件以及肿瘤富集的ASE，我们开发了CASEDI，这是一个通过整合ASE与临床数据来优先排序癌症驱动因子的计算框架。CASEDI揭示了在PCa中表现出反复ASE和表达改变的基因，包括受AR调控且具致癌性的ACSM1。与局限性肿瘤相比，mCRPC样本表现出DNA修复、耐药通路和癌基因中ASE的富集，以及单等位基因表达(MAE)频率的增加。我们基于MAE状态定义了一个mCRPC基因特征，该特征可识别出预后较差的局限性患者亚群。通过ASE分析，我们扩展了PCa中顺式调控事件的图谱，为鉴定更多治疗靶点提供依据。
查看英文原文 English abstract
The effects of cis-regulatory alterations in prostate cancer (PCa) are insufficiently characterized, presenting an opportunity to discover driver genes and therapeutic targets. To comprehensively study these effects, we identify genes undergoing allele-specific expression (ASE) in localized PCa and metastatic castration-resistant PCa (mCRPC) samples. By defining recurrent ASE events across prostate tissue and tumor-enriched ASE, we develop CASEDI, a computational framework for prioritizing cancer drivers by integrating ASE and clinical data. CASEDI reveals genes showing recurrent ASE and altered expression in PCa, including AR-regulated and oncogenic ACSM1. mCRPC samples show enrichment of ASE in DNA repair, resistance pathways, and oncogenes and increased frequency of monoallelic expression (MAE) compared to localized tumors. We define an mCRPC gene signature based on MAE status that identifies a subgroup of localized patients with worse prognosis. Using ASE analysis, we expand the landscape of cis-regulatory events in PCa to inform the identification of additional therapeutic targets.
利益披露 Disclosure
M. Tsui, None..
K. Hu, None..
S. Hsu, None..
R. Chen, None..
L. Nuniz, None..
J. Pham, None..
C. Chang, None..
K. Hui, None..
D. Quigley, None..
J. Li, None..
F. Huang, None.