Fang Fujin, Liu Chengyou, Li Qiong, Xu Rui, Zhang Tiantian, Shen Xiaobing
Key Laboratory of Environmental Medical Engineering and Education Ministry, School of Public Health, Southeast University, Nanjing, China.
Department of Preventive Medicine, School of Public Health, Southeast University, Nanjing, China.
Front Oncol. 2022 Jul 11;12:908943. doi: 10.3389/fonc.2022.908943. eCollection 2022.
Gastric 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.
We 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.
We 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.
SETBP1 may play a dual role in GC progression.
胃癌（GC）在全球范围内仍然是一种常见疾病，预后较差。SET结合蛋白1（SETBP1）与多种癌症的发病机制有关，作为癌基因和肿瘤抑制基因发挥双重作用。然而，SETBP1在胃癌中的作用及潜在机制仍不清楚。
我们使用来自癌症基因组图谱（TCGA）的下一代RNA测序（RNA-seq）数据来探索SETBP1表达与肿瘤进展之间的相关性。然后，我们通过实时定量聚合酶链反应（RT-qPCR）对胃癌细胞中的SETBP1表达进行定量。卡方检验和逻辑回归用于评估SETBP1表达与临床病理特征之间的相关性。Kaplan-Meier生存分析和Cox比例风险回归模型用于评估SETBP1表达与生存之间的关系。最后，基因集富集分析（GSEA）用于检查SETBP1表达高低的样本中与胃癌相关的信号通路。
我们发现TCGA数据库中胃癌组织中的SETBP1表达水平显著低于相邻的非肿瘤组织。此外，按肿瘤分化分类的组间SETBP1表达差异显著。此外，弥漫型胃癌中的SETBP1表达显著高于肠型胃癌。然而，在病理或T分期组中差异不显著。RT-qPCR和综合荟萃分析表明，SETBP1在胃癌细胞和组织中的表达下调。有趣的是，低分化或未分化胃癌细胞中的SETBP1表达高于高分化胃癌细胞。此外，卡方检验和逻辑回归分析表明，SETBP1表达与肿瘤分化显著相关。Kaplan-Meier曲线表明，SETBP1表达相对较高的患者预后较差。多变量分析表明，SETBP1表达可能是胃癌患者总体生存不良的重要预测指标。GSEA表明，20条信号通路在SETBP1表达高低的样本中显著富集。
SETBP1可能在胃癌进展中发挥双重作用。
