鉴定与分级相关的基因并构建用于预测膀胱癌复发的可靠基因组-临床病理列线图。
Identification of grade-related genes and construction of a robust genomic-clinicopathologic nomogram for predicting recurrence of bladder cancer.
作者信息
Peng Xiqi, Wang Jingyao, Li Dongna, Chen Xuan, Liu Kaihao, Zhang Chunduo, Lai Yongqing
机构信息
Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Shenzhen.
Shantou University Medical College, Shantou, Guangdong.
出版信息
Medicine (Baltimore). 2020 Nov 20;99(47):e23179. doi: 10.1097/MD.0000000000023179.
BACKGROUND
Bladder cancer (BC) is a common tumor in the urinary system with a high recurrence rate. The individualized treatment and follow-up after surgery is the key to a successful outcome. Currently, the surveillance strategies are mainly depending on tumor stage and grade. Previous evidence has proved that tumor grade was a significant and independent risk factor of BC recurrence. Exploring the grade-related genes may provide us a new approach to predict prognosis and guide the post-operative treatment in BC patients.
METHODS
In this study, the weighted gene co-expression network analysis was applied to identify the hub gene module correlated with BC grade using GSE71576. After constructing a protein-protein interaction (PPI) network with the hub genes inside the hub gene module, we identified some potential core genes. TCGA and another independent dataset were used for further validation.
RESULTS
The results revealed that the expression of AURKA, CCNA2, CCNB1, KIF11, TTK, BUB1B, BUB1, and CDK1 were significantly higher in high-grade BC, showing a strong ability to distinguish BC grade. The expression levels of the 8 genes in normal, paracancerous, tumorous, and recurrent bladder tissues were progressively increased. By conducting survival analysis, we proved their prognostic value in predicting the recurrence of BC. Eventually, we constructed a prognostic nomogram by combining the 8-core-gene panel with clinicopathologic features, which had shown great performance in predicting the recurrence of BC.
CONCLUSION
We identified 8 core genes that revealed a significant correlation with the tumor grade as well as the recurrence of BC. Finally, we proved the value of a novel prognostic nomogram for predicting the relapse-free survival of BC patients after surgery, which could guide their treatment and follow-up.
背景
膀胱癌(BC)是泌尿系统常见肿瘤,复发率高。术后个体化治疗及随访是取得成功疗效的关键。目前,监测策略主要取决于肿瘤分期和分级。既往证据表明肿瘤分级是BC复发的重要独立危险因素。探索与分级相关的基因可能为预测BC患者预后及指导术后治疗提供新方法。
方法
本研究应用加权基因共表达网络分析,利用GSE71576鉴定与BC分级相关的枢纽基因模块。在枢纽基因模块内用枢纽基因构建蛋白质-蛋白质相互作用(PPI)网络后,我们鉴定了一些潜在的核心基因。使用TCGA和另一个独立数据集进行进一步验证。
结果
结果显示,AURKA、CCNA2、CCNB1、KIF11、TTK、BUB1B、BUB1和CDK1在高级别BC中的表达显著更高,具有很强的区分BC分级的能力。这8个基因在正常、癌旁、肿瘤及复发膀胱组织中的表达水平逐渐升高。通过生存分析,我们证明了它们在预测BC复发方面的预后价值。最终,我们将8个核心基因组合与临床病理特征相结合构建了一个预后列线图,该列线图在预测BC复发方面表现出色。
结论
我们鉴定了8个与肿瘤分级及BC复发显著相关的核心基因。最后,我们证明了一种新型预后列线图对预测BC患者术后无复发生存的价值,其可指导患者的治疗和随访。
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