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与局部晚期淋巴结阳性前列腺癌预后相关的差异表达基因的生物信息学鉴定

Bioinformatic identification of differentially expressed genes associated with prognosis of locally advanced lymph node-positive prostate cancer.

作者信息

Kudryavtseva Anna V, Lukyanova Elena N, Kharitonov Sergey L, Nyushko Kirill M, Krasheninnikov Alexey A, Pudova Elena A, Guvatova Zulfiya G, Alekseev Boris Y, Kiseleva Marina V, Kaprin Andrey D, Dmitriev Alexey A, Snezhkina Anastasiya V, Krasnov George S

机构信息

* Laboratory of Postgenomic Research, Engelhardt Institute of Molecular Biology Russian Academy of Sciences, Vavilova 32, Moscow 119991, Russian Federation.

† Federal State Budgetary Institution, National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, 4 Korolev Str., Obninsk 249036, Russian Federation.

出版信息

J Bioinform Comput Biol. 2019 Feb;17(1):1950003. doi: 10.1142/S0219720019500033.

Abstract

Prostate cancer (PCa) is one of the primary causes of cancer-related mortality in men worldwide. Patients with locally advanced PCa with metastases in regional lymph nodes are usually marked as a high-risk group. One of the chief concerns for this group is to make an informed decision about the necessity of conducting adjuvant androgen deprivation therapy after radical surgical treatment. During the oncogenic transformation and progression of the disease, the expression of many genes is altered. Some of these genes can serve as markers for diagnosis, predicting the prognosis or effectiveness of drug therapy, as well as possible therapeutic targets. We undertook bioinformatic analysis of the RNA-seq data deposited in The Cancer Genome Atlas consortium database to identify possible prognostic markers. We compared the groups with favorable and unfavorable prognosis for the cohort of patients with PCa showing lymph node metastasis (pT2N1M0, pT3N1M0, and pT4N1M0) and for the most common molecular type carrying the fusion transcript TMPRSS2-ERG. For the entire cohort, we revealed at least six potential markers (IDO1, UGT2B15, IFNG, MUC6, CXCL11, and GBP1). Most of these genes are involved in the positive regulation of immune response. For the TMPRSS2-ERG subtype, we also identified six genes, the expression of which may be associated with prognosis: TOB1, GALNT7, INAFM1, APELA, RAC3, and NNMT. The identified genes, after additional studies and validation in the extended cohort, could serve as a prognostic marker of locally advanced lymph node-positive PCa.

摘要

前列腺癌(PCa)是全球男性癌症相关死亡的主要原因之一。局部晚期且区域淋巴结有转移的PCa患者通常被标记为高危组。该组患者主要关注的问题之一是在根治性手术治疗后,就是否有必要进行辅助雄激素剥夺治疗做出明智的决定。在疾病的致癌转化和进展过程中,许多基因的表达会发生改变。其中一些基因可作为诊断标志物、预测药物治疗的预后或疗效,以及可能的治疗靶点。我们对存于癌症基因组图谱联盟数据库中的RNA测序数据进行了生物信息学分析,以确定可能的预后标志物。我们比较了前列腺癌伴淋巴结转移(pT2N1M0、pT3N1M0和pT4N1M0)患者队列以及携带融合转录本TMPRSS2-ERG的最常见分子类型患者中预后良好和不良的组。对于整个队列,我们发现了至少六个潜在标志物(IDO1、UGT2B15、IFNG、MUC6、CXCL11和GBP1)。这些基因中的大多数都参与免疫反应的正调控。对于TMPRSS2-ERG亚型,我们还鉴定出六个基因,其表达可能与预后相关:TOB1、GALNT7、INAFM1、APELA、RAC3和NNMT。在扩大队列中进行进一步研究和验证后,所鉴定的基因可作为局部晚期淋巴结阳性前列腺癌的预后标志物。

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