揭示前列腺癌的分子特征:对个性化医疗的影响。

IF 5.7 2区 生物学 Q1 BIOLOGY Biology Direct Pub Date : 2024-12-31 DOI:10.1186/s13062-024-00492-z
Massimiliano Agostini, Erica Giacobbi, Francesca Servadei, Julia Bishof, Likas Funke, Giuseppe Sica, Valentina Rovella, Marco Carilli, Valerio Iacovelli, Yufang Shi, Jianquan Hou, Eleonora Candi, Gerry Melino, Giulio Cervelli, Manuel Scimeca, Alessandro Mauriello, Pierluigi Bove
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引用次数: 0

摘要

背景:前列腺癌是欧洲男性中最常见的诊断肿瘤和第五大癌症相关死亡。尽管ERG-TMPRSS2融合、MYC扩增、PTEN缺失以及p53和BRCA2基因突变等几种基因改变在前列腺癌的发病机制中发挥了关键作用,但能够区分轻度前列腺癌和侵袭性前列腺癌或有助于前列腺癌患者预后和/或临床管理的特异性基因改变特征仍然缺失。因此,通过多组学方法,我们描述了一种携带TMPRSS2与ERG基因融合和16q染色体臂缺失的前列腺癌。结果:我们观察到KDM6A基因的缺失,这可能代表了一个额外的基因组改变,需要考虑患者分层。癌症标志基因特征突出了有趣的分子方面,这些方面通过高缺氧和免疫浸润评分来表征这种肿瘤的生物学特征。此外,我们的分析显示肿瘤突变负担略有增加,以及免疫检查点的过度表达。结合缺氧、ROS和抗癌免疫反应的组学分析,优化治疗策略,推进前列腺癌患者的个性化护理。结论:本文报道的数据为预测所研究前列腺癌的不良预后奠定了基础,并为基于缺氧、ROS和抗癌免疫反应调节的靶向治疗奠定了基础。
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Unveiling the molecular profile of a prostate carcinoma: implications for personalized medicine.

Background: Prostate cancer is the most common diagnosed tumor and the fifth cancer related death among men in Europe. Although several genetic alterations such as ERG-TMPRSS2 fusion, MYC amplification, PTEN deletion and mutations in p53 and BRCA2 genes play a key role in the pathogenesis of prostate cancer, specific gene alteration signature that could distinguish indolent from aggressive prostate cancer or may aid in patient stratification for prognosis and/or clinical management of patients with prostate cancer is still missing. Therefore, here, by a multi-omics approach we describe a prostate cancer carrying the fusion of TMPRSS2 with ERG gene and deletion of 16q chromosome arm.

Results: We have observed deletion of KDM6A gene, which may represent an additional genomic alteration to be considered for patient stratification. The cancer hallmarks gene signatures highlight intriguing molecular aspects that characterize the biology of this tumor by both a high hypoxia and immune infiltration scores. Moreover, our analysis showed a slight increase in the Tumoral Mutational Burden, as well as an over-expression of the immune checkpoints. The omics profiling integrating hypoxia, ROS and the anti-cancer immune response, optimizes therapeutic strategies and advances personalized care for prostate cancer patients.

Conclusion: The here data reported can lay the foundation for predicting a poor prognosis for the studied prostate cancer, as well as the possibility of targeted therapies based on the modulation of hypoxia, ROS, and the anti-cancer immune response.

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来源期刊
Biology Direct
Biology Direct 生物-生物学
CiteScore
6.40
自引率
10.90%
发文量
32
审稿时长
7 months
期刊介绍: Biology Direct serves the life science research community as an open access, peer-reviewed online journal, providing authors and readers with an alternative to the traditional model of peer review. Biology Direct considers original research articles, hypotheses, comments, discovery notes and reviews in subject areas currently identified as those most conducive to the open review approach, primarily those with a significant non-experimental component.
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