Table_1_The Role of SETBP1 in Gastric Cancer: Friend or Foe.pdf

BackgroundGastric cancer (GC) remains a common disease with a poor prognosis worldwide. The SET binding protein 1 (SETBP1) has been implicated in the pathogenesis of several cancers and plays a dual role as an oncogene and a tumor suppressor gene. However, the role and underlying mechanism of SETBP1 in GC remain unclear.
Materials and MethodsWe used next-generation RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) to explore the correlation between SETBP1 expression and tumor progression. We then quantified SETBP1 expression in GC cells with real-time quantitative polymerase chain reactions (RT-qPCR). The chi-square test and logistic regression were used to assess the correlation between SETBP1 expression and clinicopathological features. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to assess the relationship between SETBP1 expression and survival. Finally, gene set enrichment analyses (GSEA) were used to examine GC-related signaling pathways in low and high SETBP1 expressing samples.
ResultsWe found SETBP1 expression levels in GC tissues to be significantly lower than in adjacent non-tumor tissues in the TCGA database. In addition, SETBP1 expression differed significantly between groups classified by tumor differentiation. Furthermore, SETBP1 expression in diffuse-type GC was significantly higher than in intestinal-type GC. However, it did not differ significantly across pathological- or T-stage groups. RT-qPCR and comprehensive meta-analysis showed that SETBP1 expression is downregulated in GC cells and tissues. Interestingly, SETBP1 expression in poorly- or un-differentiated GC cells was higher than in well-differentiated GC cells. Moreover, the chi-square test and logistic regression analyses showed that SETBP1 expression correlates significantly with tumor differentiation. Kaplan–Meier curves indicated that patients with relatively high SETBP1 expression had a poor prognosis. Multivariate analyses indicated that SETBP1 expression might be an important predictor of poor overall survival in GC patients. GSEA indicated that 20 signaling pathways were significantly enriched in samples with high and low SETBP1 expression.
ConclusionSETBP1 may play a dual role in GC progression.

背景
胃癌（Gastric cancer, GC）仍是全球范围内高发且预后不良的常见疾病。SET结合蛋白1（SET binding protein 1, SETBP1）已被证实与多种癌症的发病机制密切相关，兼具癌基因与抑癌基因的双重功能。然而，SETBP1在胃癌中的具体作用及潜在分子机制目前仍不明晰。

材料与方法
本研究依托癌症基因组图谱（The Cancer Genome Atlas, TCGA）提供的下一代RNA测序（next-generation RNA sequencing, RNA-seq）数据，探究SETBP1表达水平与肿瘤进展的相关性。随后通过实时定量聚合酶链反应（real-time quantitative polymerase chain reactions, RT-qPCR）定量检测胃癌细胞中SETBP1的表达量。采用卡方检验（chi-square test）与logistic回归分析，评估SETBP1表达与临床病理特征的关联；通过Kaplan-Meier生存分析及Cox比例风险回归模型，分析SETBP1表达与患者生存的关系。最后，利用基因集富集分析（gene set enrichment analyses, GSEA）检测SETBP1高、低表达样本中与胃癌相关的信号通路。

结果
在TCGA数据库中，胃癌组织内的SETBP1表达水平显著低于邻近非肿瘤组织。此外，SETBP1的表达水平在不同肿瘤分化程度分组间存在显著差异。进一步分析显示，弥漫型胃癌的SETBP1表达水平显著高于肠型胃癌，但在不同病理分期及T分期分组中无明显差异。RT-qPCR及整合荟萃分析结果表明，胃癌细胞与组织中SETBP1的表达呈下调状态。值得注意的是，低分化或未分化胃癌细胞的SETBP1表达水平高于高分化胃癌细胞。卡方检验与logistic回归分析证实，SETBP1表达与肿瘤分化程度显著相关。Kaplan-Meier曲线分析显示，SETBP1高表达的胃癌患者预后较差；多因素分析表明，SETBP1表达或可作为胃癌患者总体生存不良的重要预测因子。GSEA结果显示，SETBP1高、低表达样本中均富集到20条显著相关的信号通路。

结论
SETBP1或在胃癌进展中发挥双重作用。