Molecular Diagnostics and Pharmacogenetics Unit, IRCCS IstitutoTumori Giovanni Paolo II, 70124 Bari, Italy.
Laboratory of Nanotechnology, IRCCS IstitutoTumori Giovanni Paolo II, 70124 Bari, Italy.
Int J Mol Sci. 2021 Feb 23;22(4):2227. doi: 10.3390/ijms22042227.
Prostate cancer is one of the most common malignancies in men. It is characterized by a high molecular genomic heterogeneity and, thus, molecular subtypes, that, to date, have not been used in clinical practice. In the present paper, we aimed to better stratify prostate cancer patients through the selection of robust long non-coding RNAs. To fulfill the purpose of the study, a bioinformatic approach focused on feature selection applied to a TCGA dataset was used. In such a way, LINC00668 and long non-coding(lnc)-SAYSD1-1, able to discriminate ERG/not-ERG subtypes, were demonstrated to be positive prognostic biomarkers in ERG-positive patients. Furthermore, we performed a comparison between mutated prostate cancer, identified as "classified", and a group of patients with no peculiar genomic alteration, named "not-classified". Moreover, LINC00920 lncRNA overexpression has been linked to a better outcome of the hormone regimen. Through the feature selection approach, it was found that the overexpression of lnc-ZMAT3-3 is related to low-grade patients, and three lncRNAs: lnc-SNX10-87, lnc-AP1S2-2, and ADPGK-AS1 showed, through a co-expression analysis, significant correlation values with potentially druggable pathways. In conclusion, the data mining of publicly available data and robust bioinformatic analyses are able to explore the unknown biology of malignancies.
前列腺癌是男性最常见的恶性肿瘤之一。它的特点是具有高度的分子基因组异质性,因此存在分子亚型,但迄今为止尚未在临床实践中应用。在本文中,我们旨在通过选择稳健的长非编码 RNA 来更好地对前列腺癌患者进行分层。为了实现研究目的,使用了一种针对 TCGA 数据集的专注于特征选择的生物信息学方法。通过这种方式,能够区分 ERG/非 ERG 亚型的 LINC00668 和长非编码(lnc)-SAYSD1-1 被证明是 ERG 阳性患者的阳性预后生物标志物。此外,我们对突变型前列腺癌(被鉴定为“分类”)和一组没有特殊基因组改变的患者(命名为“未分类”)进行了比较。此外,LINC00920 lncRNA 的过表达与激素治疗方案的更好结果相关。通过特征选择方法发现,lnc-ZMAT3-3 的过表达与低级别患者相关,并且通过共表达分析发现三个 lncRNA:lnc-SNX10-87、lnc-AP1S2-2 和 ADPGK-AS1 与潜在可成药途径具有显著的相关值。总之,对公开可用数据的挖掘和稳健的生物信息学分析能够探索恶性肿瘤的未知生物学。