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TSGA10基因表达在急性髓系白血病(AML)患者中的作用及预后价值。

Contribution and prognostic value of TSGA10 gene expression in patients with acute myeloid leukemia (AML).

作者信息

Hoseinkhani Zohreh, Rastegari-Pouyani Mohsen, Oubari Farhad, Mozafari Hadi, Rahimzadeh Amir Bahman, Maleki Ali, Amini Saeideh, Mansouri Kamran

机构信息

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Student Research Committee, Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Pathol Res Pract. 2019 Mar;215(3):506-511. doi: 10.1016/j.prp.2019.01.003. Epub 2019 Jan 7.

Abstract

BACKGROUND

Different studies have investigated TSGA10 expression in various cancerous tissues but, so far no study has been conducted on newly diagnosed (ND) AML patients. The association of TSGA10 gene expression with hypoxia inducible factor (HIF) and angiogenic factors has remained to be fully elucidated and is still a controversial issue. The present study was designed to investigate this association in patients newly diagnosed with AML.

METHODS

We evaluated TSGA10, HIF-1α and VEGF mRNA levels in ND AML patients and healthy subjects using real-time PCR technique. Data were analyzed via comparative Livak method.

RESULTS

Based on the results of this study, TSGA10 gene expression was decreased in 28 out of 30 (93.3%) samples while VEGF and HIF-1α expression levels were increased in all ND AML patients compared to healthy controls. Diagnostic evaluation was performed by receiver operating characteristic (ROC) curve and area under the curve (AUC) calculation. Respectively, using cut-off relative quantification of 1.604, 0.0329, and 0.0042, the sensitivity values of TSGA10, VEGF, and HIF-1α gene expression were 86.7%, 90%, and 100%. Also, specificity values were 100%, 100% and 100%, respectively. TSGA10 expression was shown to be reduced in ND AML patients compared with healthy subjects and we found a negative correlation between TSGA10 and VEGF expression.

CONCLUSIONS

Since TSGA10 interacts with HIF-1 and affects its transcriptional activity, in ND AML patients with decreased TSGA10 expression, VEGF expression was high suggesting a TSGA10 mediated regulation of HIF-1 target genes. Altogether, the current study showed that TSGA10 could be considered as a tumor suppressor in AML patients.

摘要

背景

不同的研究已经调查了TSGA10在各种癌组织中的表达,但迄今为止,尚未对新诊断的(ND)急性髓系白血病(AML)患者进行研究。TSGA10基因表达与缺氧诱导因子(HIF)和血管生成因子之间的关联仍有待充分阐明,并且仍然是一个有争议的问题。本研究旨在调查新诊断的AML患者中的这种关联。

方法

我们使用实时PCR技术评估了ND AML患者和健康受试者中TSGA10、HIF-1α和VEGF mRNA水平。数据通过比较Livak方法进行分析。

结果

基于本研究的结果,30个样本中有28个(93.3%)的TSGA10基因表达降低,而与健康对照相比,所有ND AML患者的VEGF和HIF-1α表达水平均升高。通过受试者工作特征(ROC)曲线和曲线下面积(AUC)计算进行诊断评估。分别使用截断相对定量1.604、0.0329和0.0042,TSGA10、VEGF和HIF-1α基因表达的敏感性值分别为86.7%、90%和100%。此外,特异性值分别为100%、100%和100%。与健康受试者相比,ND AML患者中TSGA10表达降低,并且我们发现TSGA10与VEGF表达之间存在负相关。

结论

由于TSGA10与HIF-1相互作用并影响其转录活性,在TSGA10表达降低的ND AML患者中,VEGF表达较高,提示TSGA10介导对HIF-1靶基因的调控。总之,当前研究表明TSGA10可被视为AML患者中的一种肿瘤抑制因子。

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