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前列腺癌晚期进展过程中的基因表达变化及相关通路

Gene Expression Changes and Associated Pathways Involved in the Progression of Prostate Cancer Advanced Stages.

作者信息

Pudova Elena A, Krasnov George S, Kobelyatskaya Anastasiya A, Savvateeva Maria V, Fedorova Maria S, Pavlov Vladislav S, Nyushko Kirill M, Kaprin Andrey D, Alekseev Boris Y, Trofimov Dmitry Y, Sukhikh Gennady T, Snezhkina Anastasiya V, Kudryavtseva Anna V

机构信息

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.

National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow, Russia.

出版信息

Front Genet. 2021 Jan 21;11:613162. doi: 10.3389/fgene.2020.613162. eCollection 2020.

Abstract

Prostate cancer (PC) is one of the most common cancers among men worldwide, and advanced PCs, such as locally advanced PC (LAPC) and castration-resistant PC (CRPC), present the greatest challenges in clinical management. Current indicators have limited capacity to predict the disease course; therefore, better prognostic markers are greatly needed. In this study, we performed a bioinformatic analysis of The Cancer Genome Atlas (TCGA) datasets, including RNA-Seq data from the prostate adenocarcinoma (PRAD; = 55) and West Coast Dream Team - metastatic CRPC (WCDT-MCRPC; = 84) projects, to evaluate the transcriptome changes associated with progression-free survival (PFS) for LAPC and CRPC, respectively. We identified the genes whose expression was positively/negatively correlated with PFS. In LAPC, the genes with the most significant negative correlations were , , and , and the genes with the most significant positive correlations were , , , , and . In CRPC, the most significant positive correlations were found for , , , and , and the most significant negative correlations were found for , , , , and . In addition, we performed a gene network interaction analysis using STRINGdb, which revealed a significant relationship between genes predominantly involved in the cell cycle and characterized by upregulated expression in early recurrence. Based on the results, we propose several genes that can be used as potential prognostic markers.

摘要

前列腺癌(PC)是全球男性中最常见的癌症之一,而晚期前列腺癌,如局部晚期前列腺癌(LAPC)和去势抵抗性前列腺癌(CRPC),在临床管理中面临着最大的挑战。目前的指标预测疾病进程的能力有限;因此,非常需要更好的预后标志物。在本研究中,我们对癌症基因组图谱(TCGA)数据集进行了生物信息学分析,包括来自前列腺腺癌(PRAD;n = 55)和西海岸梦之队 - 转移性CRPC(WCDT - MCRPC;n = 84)项目的RNA测序数据,以分别评估与LAPC和CRPC的无进展生存期(PFS)相关的转录组变化。我们鉴定了其表达与PFS呈正相关/负相关的基因。在LAPC中,与PFS负相关最显著的基因是 、 和 ,与PFS正相关最显著的基因是 、 、 、 和 。在CRPC中, 、 、 和 与PFS的正相关最显著, 、 、 、 和 与PFS的负相关最显著。此外,我们使用STRINGdb进行了基因网络相互作用分析,结果显示主要参与细胞周期且在早期复发中表达上调的基因之间存在显著关系。基于这些结果,我们提出了几个可作为潜在预后标志物的基因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e2e/7859645/89c0082a13b3/fgene-11-613162-g001.jpg

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