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高着丝粒蛋白A(CENP-A)表达与胃癌的进展及预后相关。

High Centromere Protein-A (CENP-A) Expression Correlates with Progression and Prognosis in Gastric Cancer.

作者信息

Xu Yuan, Liang Chao, Cai Xianlei, Zhang Miaozun, Yu Weiming, Shao Qinshu

机构信息

Department of Gastrointestinal Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo 315000, People's Republic of China.

Department of Gastrointestinal Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Dec 29;13:13237-13246. doi: 10.2147/OTT.S263512. eCollection 2020.

Abstract

PURPOSE

Recent studies have established the ability of centromere protein-A (CENP-A) to perform as an oncogene, regulating tumor progression. The aim of this research was to explore the relationship between CENP-A expression and clinical significance in gastric cancer (GC) patients.

MATERIALS AND METHODS

Experiments with a microarray were conducted using the Affymetrix U133 plus 2.0 GeneChip Array. Upregulated differentially expressed genes (DEGs) were identified via the GEO2R and intersected using a Venn diagram. Bioinformatic databases Omcomine, GEPIA, and Ualcan were applied to investigate the expression level of CENP-A in GC. The real-time quantitative RT-PCR (qRT-PCR) was used to validate the level of CENP-A mRNA in GC. Immunohistochemistry (IHC) was employed to verify the protein levels of CENP-A, while the relationship between CENP-A expression and patients' clinical parameters in GC was explored through the use of IHC. Kaplan-Meier analysis was conducted to evaluate the prognostic significance of CENP-A. Additionally, the Kaplan-Meier plotter database (KM plotter) was used to verify the prognostic function of CENP-A in GC patients.

RESULTS

The results indicated that CENP-A was significantly overexpressed, both in protein and mRNA levels of GC tissues, compared to adjacent noncancerous tissues (P<0.05). Furthermore, we observed that CENP-A expression was positively associated with TNM stage, tumor classification, lymph node metastasis, distant metastasis, and Lauren type (P<0.05). Kaplan-Meier analysis showed that patients with an overexpression of CENP-A had significantly poorer overall survival (OS) times (P<0.05). Multivariate analysis suggested CENP-A may serve as an independent predicting factor for the poor outcome of GC patients.

CONCLUSION

Our results show that CENP-A upregulation is significantly correlated with advanced tumor progression and poor prognosis. CENP-A may function as a novel potential biomarker for predicting the clinical outcomes of GC patients.

摘要

目的

近期研究证实着丝粒蛋白A(CENP-A)具有癌基因功能,可调节肿瘤进展。本研究旨在探讨CENP-A表达与胃癌(GC)患者临床意义之间的关系。

材料与方法

使用Affymetrix U133 plus 2.0基因芯片进行微阵列实验。通过GEO2R鉴定上调的差异表达基因(DEG),并用维恩图进行交集分析。应用生物信息学数据库Omcomine、GEPIA和Ualcan研究GC中CENP-A的表达水平。采用实时定量逆转录PCR(qRT-PCR)验证GC中CENP-A mRNA的水平。采用免疫组织化学(IHC)验证CENP-A的蛋白水平,同时通过IHC探讨CENP-A表达与GC患者临床参数之间的关系。进行Kaplan-Meier分析以评估CENP-A的预后意义。此外,使用Kaplan-Meier绘图仪数据库(KM绘图仪)验证CENP-A在GC患者中的预后功能。

结果

结果表明,与相邻的非癌组织相比,GC组织的蛋白质和mRNA水平上CENP-A均显著过表达(P<0.05)。此外,我们观察到CENP-A表达与TNM分期、肿瘤分级、淋巴结转移、远处转移和Lauren分型呈正相关(P<0.05)。Kaplan-Meier分析表明,CENP-A过表达的患者总生存期(OS)显著较差(P<0.05)。多因素分析表明,CENP-A可能是GC患者预后不良的独立预测因素。

结论

我们的结果表明,CENP-A上调与肿瘤进展和预后不良显著相关。CENP-A可能作为预测GC患者临床结局的新型潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ee/7778524/36c48771e9d3/OTT-13-13237-g0001.jpg

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