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AKRs 超家族在人胃癌中的表达与预后。

Expression of AKRs superfamily and prognostic in human gastric cancer.

机构信息

NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China.

Laboratory Medicine Center of Huazhong University of Science and Technology Union Shenzhen Hospital (Nanshan Hospital), Shenzhen, China.

出版信息

Medicine (Baltimore). 2023 Feb 22;102(8):e33041. doi: 10.1097/MD.0000000000033041.

Abstract

The human aldo-keto reductase (AKRs) superfamily is involved in the development of various tumors. However, the different expression patterns of AKRs and their prognostic value in gastric cancer (GC) have not been clarified. In this study, we analyzed the gene expression and gene methylation level of AKRs in GC patients and the survival data and immune infiltration based on AKRs expression, using data from different databases. We found that the expression levels of AKR1B10, AKR1C1, AKR1C2, and AKR7A3 in GC tissues were lower and the expression level of AKR6A5 was higher in GC tissues than in normal tissue. These differentially expressed genes (AKR1B10, AKR1C1, AKR1C2, AKR7A3, and AKR6A5) were significantly correlated with the infiltration level. The expression of SPI1 and AKR6A5 in GC was positively correlated. Survival analysis showed that GC levels of AKR6A5 reduced or increased mRNA levels of AKR7A3, and AKR1B10 was expected to have higher overall survival (OS), first progression (FP) survival, and postprogression survival (PPS) rates and a better prognosis. Moreover, the expression of AKR1B1 was found to be correlated with the staging of GC. The methylation of AKR6A5 (KCNAB2) at cg05307871 and cg01907457 was significantly associated with the classification of GC. Meta-analysis and ROC curve analysis show that the expression level of AKR1B1 and the methylation of cg16156182 (KCNAB1), cg11194299 (KCNAB2), cg16132520 (AKR1B1), and cg13801416 (AKR1B1) had a high hazard ratio and a good prognostic value. These data suggest that the expression and methylation of AKR1B1 and AKR6A5 are significantly related to the prognosis.

摘要

人类醛酮还原酶(AKR)超家族参与了各种肿瘤的发生。然而,AKR 在胃癌(GC)中的不同表达模式及其预后价值尚未阐明。在本研究中,我们利用来自不同数据库的 GC 患者的基因表达和基因甲基化水平以及生存数据和免疫浸润数据,分析了 AKR 的基因表达。我们发现,与正常组织相比,GC 组织中 AKR1B10、AKR1C1、AKR1C2 和 AKR7A3 的表达水平较低,而 AKR6A5 的表达水平较高。这些差异表达基因(AKR1B10、AKR1C1、AKR1C2、AKR7A3 和 AKR6A5)与浸润水平显著相关。GC 中 SPI1 和 AKR6A5 的表达呈正相关。生存分析表明,GC 中 AKR6A5 降低或增加 AKR7A3 的 mRNA 水平,AKR1B10 预期具有更高的总生存期(OS)、首次进展(FP)生存期和进展后生存期(PPS)率和更好的预后。此外,AKR1B1 的表达与 GC 的分期有关。AKR6A5(KCNAB2)在 cg05307871 和 cg01907457 处的甲基化与 GC 的分类显著相关。荟萃分析和 ROC 曲线分析表明,AKR1B1 的表达水平和 cg16156182(KCNAB1)、cg11194299(KCNAB2)、cg16132520(AKR1B1)和 cg13801416(AKR1B1)的甲基化水平具有较高的危险比和良好的预后价值。这些数据表明,AKR1B1 和 AKR6A5 的表达和甲基化与预后显著相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e63/11309706/528d8bd7ed8c/medi-102-e33041-g001.jpg

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