Table_1_Differentially Expressed Genes Associated With Prognosis in Locally Advanced Lymph Node-Negative Prostate Cancer.xls

Older age is one of the main risk factors for cancer development. The incidence of prostate cancer, as a multifactorial disease, also depends upon demographic factors, race, and genetic predisposition. Prostate cancer most frequently occurs in men over 60 years of age, indicating a clear association between older age and disease onset. Carcinogenesis is followed by the deregulation of many genes, and some of these changes could serve as biomarkers for diagnosis, prognosis, prediction of drug therapy efficacy, as well as possible therapeutic targets. We have performed a bioinformatic analysis of a The Cancer Genome Atlas (TCGA) data and RNA-Seq profiling of a Russian patient cohort to reveal prognostic markers of locally advanced lymph node-negative prostate cancer (lymph node-negative LAPC). We also aimed to identify markers of the most common molecular subtype of prostate cancer carrying a fusion transcript TMPRSS2-ERG. We have found several genes that were differently expressed between the favorable and unfavorable prognosis groups and involved in the enriched KEGG pathways based on the TCGA (B4GALNT4, PTK6, and CHAT) and Russian patient cohort data (AKR1C1 and AKR1C3). Additionally, we revealed such genes for the TMPRSS2-ERG prostate cancer molecular subtype (B4GALNT4, ASRGL1, MYBPC1, RGS11, SLC6A14, GALNT13, and ST6GALNAC1). Obtained results contribute to a better understanding of the molecular mechanisms behind prostate cancer progression and could be used for further development of the LAPC prognosis marker panel.

衰老是癌症发生的主要风险因素之一。前列腺癌作为多因素疾病，其发病率同时受人口统计学特征、种族与遗传易感性影响。前列腺癌高发于60岁以上男性，提示高龄与疾病发病存在明确关联。癌变进程伴随大量基因的表达失调，其中部分异常变化可作为诊断、预后评估、药物治疗疗效预测的生物标志物，亦可能成为潜在治疗靶点。本研究针对癌症基因组图谱（The Cancer Genome Atlas, TCGA）数据集与俄罗斯患者队列的RNA测序（RNA-Seq）表达谱开展生物信息学分析，以挖掘局部晚期淋巴结阴性前列腺癌（lymph node-negative LAPC）的预后标志物。同时，本研究亦旨在鉴定携带融合转录本TMPRSS2-ERG的前列腺癌最常见分子亚型的相关标志物。研究团队基于TCGA数据集与俄罗斯患者队列数据，分别筛选出预后良好组与预后不良组间存在差异表达且富集于KEGG通路的基因：其中TCGA数据集相关基因为B4GALNT4、PTK6与CHAT，俄罗斯患者队列相关基因为AKR1C1与AKR1C3。此外，本研究还鉴定出针对TMPRSS2-ERG前列腺癌分子亚型的关联基因，包括B4GALNT4、ASRGL1、MYBPC1、RGS11、SLC6A14、GALNT13及ST6GALNAC1。本研究结果有助于深化对前列腺癌进展分子机制的理解，可为后续开发局部晚期淋巴结阴性前列腺癌的预后标志物组合提供理论支撑。