Development and Validation of a Scoring System Based on 9 Glycolysis-Related Genes for Prognosis Prediction in Gastric Cancer.

Development and Validation of a Scoring System Based on 9 Glycolysis-Related Genes for Prognosis Prediction in Gastric Cancer.
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DOI:
10.1177/1533033820971670
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发表时间:
2020-01
影响因子:
2.8
通讯作者:
Chen Y
Chen Y
中科院分区:
医学4区
文献类型:
--
作者:
Luo T;Du Y;Duan J;Liang C;Chen G;Jiang K;Chen Y;Chen Y

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胃癌是世界范围内发病率和死亡率都很高的恶性肿瘤。然而,越来越多的证据表明糖酵解过程与肿瘤发生之间存在相关性。本研究的目的是建立一个糖酵解相关基因的列表,用于胃癌患者的危险分层。我们纳入了来自GSE 62254和GSE 26942数据集的500例患者样本数据,并将患者以7:3的比例分为训练集(n = 350)和测试集(n = 150)。单因素和多因素考克斯回归分析筛选具有预后价值的基因。基于HALLMARK基因集,我们鉴定了9个糖酵解相关基因(BPNT 1、DCN、FUT 8、GMPPA、GPC 3、LDHC、ME 2、PLOD 2和UGP 2)。根据9个基因的风险评分,将患者分为高风险组和低风险组。生存分析显示,高危患者预后较差(P < 0.001)。在测试组群和2个独立组群中观察到类似的发现(GSE 13861和TCGA-STAD,所有p < 0.001)。多因素考克斯回归分析显示,危险评分是影响总生存率的独立预后因素(p < 0.001)。此外,我们构建了一个诺模图,整合了风险评分和肿瘤分期,年龄和辅助化疗。通过受试者工作特征曲线和决策曲线分析结果的比较,我们发现诺模图的预测准确性上级传统的TNM分期系统,提示风险评分结合其他临床因素(年龄、肿瘤分期和辅助化疗)可以建立一个稳健的生存预测模型,提高患者的个体化临床决策。总之,我们从糖酵解途径中鉴定出9个糖酵解相关基因。根据这9个基因,胃癌患者被分为与生存相关的不同风险组。
Gastric cancer is a malignant tumor with high morbidity and mortality worldwide. However, increasing evidences have revealed the correlation between the glycolysis process and tumorigenesis. This study is aim to develop a list of glycolysis-related genes for risk stratification in gastric cancer patients. We included 500 patients’ sample data from GSE62254 and GSE26942 datasets, and classified patients into training (n = 350) and testing sets (n = 150) at a ratio of 7: 3. Univariate and multivariate Cox regression analysis were performed to screen genes having prognostic value. Based on HALLMARK gene sets, we identified 9 glycolysis-related genes (BPNT1, DCN, FUT8, GMPPA, GPC3, LDHC, ME2, PLOD2, and UGP2). On the basis of risk score developed by the 9 genes, patients were classified into high- and low-risk groups. The survival analysis showed that the high-risk patients had a worse prognosis (p < 0.001). Similar finding was observed in the testing cohort and 2 independent cohorts (GSE13861 and TCGA-STAD, all p < 0.001). The multivariate Cox regression analysis showed that the risk score was an independent prognostic factor for overall survival (p < 0.001). Furthermore, we constructed a nomogram that integrated the risk score and tumor stage, age, and adjuvant chemotherapy. Through comparing the results of the receiver operating characteristic curves and decision curve analysis, we found that the nomogram had a superior predictive accuracy than conventional TNM staging system, suggesting that the risk score combined with other clinical factors (age, tumor stage, and adjuvant chemotherapy) can develop a robust prediction for survival and improve the individualized clinical decision making of the patient. In conclusion, we identified 9 glycolysis-related genes from hallmark glycolysis pathway. Based on the 9 genes, gastric cancer patients were separated into different risk groups related to survival.
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