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Discovery of Prognostic Signature Genes for Overall Survival Prediction in Gastric Cancer

机译:胃癌总生存预测的预后签名基因发现

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Background. Gastric cancer (GC) is one of the most common malignant tumors in the digestive system with high mortality globally. However, the biomarkers that accurately predict the prognosis are still lacking. Therefore, it is important to screen for novel prognostic markers and therapeutic targets. Methods. We conducted differential expression analysis and survival analysis to screen out the prognostic genes. A stepwise method was employed to select a subset of genes in the multivariable Cox model. Overrepresentation enrichment analysis (ORA) was used to search for the pathways associated with poor prognosis. Results. In this study, we designed a seven-gene-signature-based Cox model to stratify the GC samples into high-risk and low-risk groups. The survival analysis revealed that the high-risk and low-risk groups exhibited significantly different prognostic outcomes in both the training and validation datasets. Specifically, CGB5, IGFBP1, OLFML2B, RAI14, SERPINE1, IQSEC2, and MPND were selected by the multivariable Cox model. Functionally, PI3K-Akt signaling pathway and platelet-derived growth factor receptor (PDGFR) were found to be hyperactive in the high-risk group. The multivariable Cox regression analysis revealed that the risk stratification based on the seven-gene-signature-based Cox model was independent of other prognostic factors such as TNM stages, age, and gender. Conclusion. In conclusion, we aimed at developing a model to predict the prognosis of gastric cancer. The predictive model could not only effectively predict the risk of GC but also be beneficial to the development of therapeutic strategies.
机译:背景。胃癌(GC)是在全球死亡率高的消化系统中最常见的恶性肿瘤之一。然而,准确预测预后的生物标志物仍然缺乏。因此,重要的是筛选新型预后标志物和治疗靶标。方法。我们进行了差异表达分析和生存分析,以筛选预后基因。采用逐步方法选择多变量COX模型中基因的子集。过度陈述富集分析(ORA)用于搜索与预后差相关的途径。结果。在这项研究中,我们设计了一种基于七基因签名的Cox模型,以将GC样本分为高风险和低风险群体。生存分析表明,高风险和低风险群体在培训和验证数据集中表现出显着不同的预后结果。具体而言,通过多变量Cox模型选择CGB5,IGFBP1,OLFML2B,RAI14,Serpine1,IQSEC2和MPND。在功能上,发现PI3K-AKT信号传导途径和血小板衍生的生长因子受体(PDGFR)在高风险组中具有过度活跃。多变量的Cox回归分析显示,基于七基因签名的Cox模型的风险分层与其他预后因素(如TNM阶段,年龄和性别)无关。结论。总之,我们旨在开发一种模型来预测胃癌的预后。预测模型不仅可以有效地预测GC的风险,而且有利于治疗策略的发展。

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