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A novel risk score based on a combined signature of 10 immune system genes to predict bladder cancer prognosis.
International Immunopharmacology ( IF 4.8 ) Pub Date : 2020-08-05 , DOI: 10.1016/j.intimp.2020.106851
Yunliang Tang 1 , Yangyang Hu 2 , Jiao Wang 3 , Zhenguo Zeng 4
Affiliation  

Bladder cancer (BC) is a common internal malignant tumor with a poor prognosis worldwide. There is an urgent need to better understand the pathogenesis and progression of BC and to find useful biomarkers for diagnosis and prognosis. This study was aimed at developing a potential immunogenomic prognostic signature for BC patients. To identify possible immune-system-related genes (IRGs) whose parameters predict the survival of BC patients, we chose 371 BC patients and analyzed differentially expressed IRGs from The Cancer Genome Atlas (TCGA) datasets. We then derived a 10-IRG formula, including MMP9, RBP7, PDGFRA, AHNAK, OAS1, OLR1, RAC3, SLIT2, IGF1, and AGTR1, to estimate BC prognosis. To validate the mRNA levels of these IRGs, we performed quantitative PCR and found that the expression of these genes almost matched the corresponding mRNA expression levels in TCGA. Furthermore, we validated the prognostic value of the new risk model using two external datasets from Gene Expression Omnibus: GSE13507 (n = 165) and GSE32894 (n = 224). Our data pointed to a significant correlation between the risk model and patients’ prognosis. Bioinformatic analysis revealed that products of the IRGs have possible effects on tumor immune processes such as an inflammatory response and cytokine-cytokine receptor interaction. Finally, assessment of the clinical value of the immune-system–based risk signature showed that several of these IRGs were differentially expressed between patients with different clinical characteristics: a high risk score positively correlated with female sex, advanced tumor stage, more advanced T stage, and lymph node metastasis. This immunogenomic signature may represents a reliable prognostic tool for BC and can help to design an individualized immunotherapy.



中文翻译:

基于10个免疫系统基因的组合特征的新型风险评分,可预测膀胱癌的预后。

膀胱癌(BC)是一种常见的内部恶性肿瘤,在全世界范围内预后较差。迫切需要更好地了解BC的发病机理和进展,并找到有用的生物标记物用于诊断和预后。这项研究旨在为BC患者开发潜在的免疫基因组预后标志。为了确定可能的免疫系统相关基因(IRGs),这些参数可预测BC患者的生存,我们选择了371例BC患者,并从癌症基因组图谱(TCGA)数据集中分析了差异表达的IRG。然后,我们导出了10-IRG公式,包括MMP9RBP7PDGFRAAHNAKOAS1OLR1RAC3SLIT2IGF1AGTR1,以估计BC预后。为了验证这些IRG的mRNA水平,我们进行了定量PCR,发现这些基因的表达几乎与TCGA中相应的mRNA表达水平匹配。此外,我们使用来自Gene Expression Omnibus的两个外部数据集验证了新风险模型的预后价值:GSE13507(n = 165)和GSE32894(n = 224)。我们的数据表明,风险模型与患者预后之间存在显着相关性。生物信息学分析表明,IRG的产物可能对肿瘤免疫过程产生影响,例如炎症反应和细胞因子与细胞因子受体的相互作用。最后,对基于免疫系统的风险特征的临床价值进行的评估表明,这些IRG中有几种在具有不同临床特征的患者之间差异表达:高风险评分与女性,肿瘤晚期,更晚期T期和淋巴结转移。这种免疫基因组特征可以代表BC可靠的预后工具,并且可以帮助设计个性化的免疫疗法。

更新日期:2020-08-05
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