A novel gene signature combination improves the prediction of overall survival in urinary bladder cancer
A novel gene signature combination improves the prediction of overall survival in urinary bladder cancer
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一种新的基因特征组合提高了膀胱癌总体生存率的预测
DOI：
10.7150/jca.30307
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发表时间：
2019-01-01
影响因子：
3.9
通讯作者：
Wang, Xiang
中科院分区：
文献类型：
--
作者：
Chen, Siteng;Zhang, Ning;Wang, Xiang
目的：膀胱癌是一种临床异质性疾病，其预后存在显着差异且死亡风险较高。这突出表明需要识别高效的癌症特征来预测临床预后。方法：本研究对基因表达综合数据集中的 93 名膀胱肿瘤患者以及从癌症基因组图谱数据库中检索的 408 名膀胱肿瘤患者进行了基因表达谱分析。在训练队列中分析了基因特征和总体生存率的关系 (n = 46)。对此的验证是在内部验证队列 (n = 47) 和外部验证队列 (n = 408) 中进行的。结果：通过单变量和多变量 Cox 回归分析鉴定出四个基因（TMPRSS11E、SCEL、KRT78、TMEM185A）。根据基于四基因特征的风险评分，我们将这些患者分为高风险组和低风险组，在训练系列中总体生存率显着不同，并在内部和外部验证队列中成功进行了验证。随后的研究表明，四基因表达风险评分与根治性膀胱切除术分期、化疗和淋巴结状态无关。与低风险评分的膀胱肿瘤相比，高风险评分的膀胱肿瘤的 FAT4 突变和 MACF1 突变率较高。基因集富集分析显示高风险评分与一些肿瘤进展和复发相关途径相关。结论：这种四基因风险评分可能对选择高危膀胱癌患者进行积极治疗具有潜在的临床意义。所选的四个基因可能成为膀胱癌的潜在治疗靶点和诊断标志物。
Objectives: Bladder carcinoma is a clinical heterogeneous disease, which is with significant variability of the prognosis and high risk of death. This revealed prominently the need to identify high-efficiency cancer characteristics to predict clinical prognosis. Methods: Gene expression profiles of 93 bladder tumor patients from Gene Expression Omnibus data sets was performed in this study, along with 408 bladder tumor patients retrieved from The Cancer Genome Atlas database. The relationship of gene signature and overall survival was analyzed in the training cohort (n = 46). The validation for that was performed in an internal validation cohort (n = 47) and an external validation cohort (n = 408). Results: Four genes (TMPRSS11E, SCEL, KRT78, TMEM185A) were identified by univariable and multivariable Cox regression analysis. According to a risk score on the bases on the four-gene signature, we grouped these patients in high-risk group and low-risk group with significantly different overall survival in the training series and successfully validated it in both the internal and external validation cohorts. Subsequent studies demonstrated that the four-gene expression risk score was independent of radical cystectomy stage, chemotherapy and lymph node status. Higher rates of FAT4 mutation and MACF1 mutation in bladder tumors with high risk score were found compared with tumors with low risk score. Gene set enrichment analysis revealed high-risk score was associated with some tumor progression and recurrence associated pathways. Conclusions: This four-gene risk score might have potential clinical implications in the selection of high-risk urinary bladder cancer patients for aggressive therapy. The selected four genes might become potential therapeutic targets and diagnostic markers for urinary bladder cancer.