Agostini Massimiliano, Giacobbi Erica, Servadei Francesca, Bishof Julia, Funke Likas, Sica Giuseppe, Rovella Valentina, Carilli Marco, Iacovelli Valerio, Shi Yufang, Hou Jianquan, Candi Eleonora, Melino Gerry, Cervelli Giulio, Scimeca Manuel, Mauriello Alessandro, Bove Pierluigi
Department of Experimental Medicine, TOR, University of Rome "Tor Vergata", Rome, 00133, Italy.
Indivumed GmbH, Falkenried, 88 Building D, 20251, Hamburg, Germany.
Biol Direct. 2024 Dec 31;19(1):146. doi: 10.1186/s13062-024-00492-z.
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.
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.
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.
前列腺癌是欧洲男性中最常被诊断出的肿瘤，也是癌症相关死亡的第五大原因。尽管一些基因改变，如ERG-TMPRSS2融合、MYC扩增、PTEN缺失以及p53和BRCA2基因的突变在前列腺癌的发病机制中起关键作用，但仍缺乏能够区分惰性与侵袭性前列腺癌，或有助于对前列腺癌患者进行预后分层和/或临床管理的特定基因改变特征。因此，在此我们通过多组学方法描述了一例携带TMPRSS2与ERG基因融合以及16号染色体臂缺失的前列腺癌。
我们观察到KDM6A基因缺失，这可能代表一种可用于患者分层的额外基因组改变。癌症特征基因特征突出了有趣的分子方面，其通过高缺氧和免疫浸润评分来表征该肿瘤的生物学特性。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表达。整合缺氧、活性氧和抗癌免疫反应的组学分析优化了治疗策略，并推动了前列腺癌患者的个性化护理。
本文报道的数据可为预测所研究前列腺癌的不良预后奠定基础，以及基于缺氧、活性氧和抗癌免疫反应调节进行靶向治疗的可能性。
