胰腺癌启动子低甲基化上调ANXA2表达并与不良预后相关

IF 2.1 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemical Genetics Pub Date : 2024-08-01 Epub Date: 2023-11-24 DOI:10.1007/s10528-023-10577-5
Soumaya Menadi, Burak Kucuk, Ercan Cacan
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引用次数: 0

摘要

胰腺癌(PC)是世界上最具侵袭性和致命性的癌症之一,由于非特异性早期临床症状,晚期诊断和生存率低。因此,确定特异性的生物标志物对早期诊断至关重要。膜联蛋白A2 (ANXA2)是一种钙依赖性磷脂结合蛋白,据报道在几种癌症类型中上调,使其成为一种新兴的生物标志物和潜在的癌症治疗靶点。然而,调控ANXA2过表达的机制尚不清楚。众所周知,遗传和表观遗传改变可能导致广泛的基因表达失调。因此,在本研究中,我们利用多个生物信息学数据库,通过研究ANXA2在PC中的转录谱、甲基化模式、体细胞突变和预后价值,重点探索ANXA2的调控机制。结果显示,与正常组织相比,PC组织中ANXA2的表达水平显著升高。此外,ANXA2的高表达与PC患者的不良预后显著相关。更重要的是,我们首次证明,与正常组织相比,PC组织中的ANXA2启动子甲基化程度较低,这可能导致PC中的ANXA2过表达。然而,需要更多的实验研究来证实我们的发现。
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Promoter Hypomethylation Upregulates ANXA2 Expression in Pancreatic Cancer and is Associated with Poor Prognosis.

Pancreatic cancer (PC) is one of the world's most aggressive and deadly cancers, owing to non-specific early clinical symptoms, late-stage diagnosis, and poor survival. Therefore, it is critical to identify specific biomarkers for its early diagnosis. Annexin A2 (ANXA2) is a calcium-dependent phospholipid-binding protein that has been reported to be upregulated in several cancer types, making it an emerging biomarker and potential cancer therapeutic target. However, the mechanism underlying the regulation of ANXA2 overexpression is still unclear. It is well established that genetic and epigenetic alterations may lead to widespread dysregulation of gene expression. Hence, in this study, we focused on exploring the regulatory mechanism of ANXA2 by investigating the transcriptional profile, methylation pattern, somatic mutation, and prognostic value of ANXA2 in PC using several bioinformatics databases. Our results revealed that the expression levels of ANXA2 were remarkably increased in PC tissues comparing to normal tissues. Furthermore, the high expression of ANXA2 was significantly related to the poor prognosis of PC patients. More importantly, we demonstrated for the first time that the ANXA2 promoter is hypomethylated in PC tissues compared to normal tissues which may result in ANXA2 overexpression in PC. However, more experimental research is required to corroborate our findings.

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来源期刊
Biochemical Genetics
Biochemical Genetics 生物-生化与分子生物学
CiteScore
3.90
自引率
0.00%
发文量
133
审稿时长
4.8 months
期刊介绍: Biochemical Genetics welcomes original manuscripts that address and test clear scientific hypotheses, are directed to a broad scientific audience, and clearly contribute to the advancement of the field through the use of sound sampling or experimental design, reliable analytical methodologies and robust statistical analyses. Although studies focusing on particular regions and target organisms are welcome, it is not the journal’s goal to publish essentially descriptive studies that provide results with narrow applicability, or are based on very small samples or pseudoreplication. Rather, Biochemical Genetics welcomes review articles that go beyond summarizing previous publications and create added value through the systematic analysis and critique of the current state of knowledge or by conducting meta-analyses. Methodological articles are also within the scope of Biological Genetics, particularly when new laboratory techniques or computational approaches are fully described and thoroughly compared with the existing benchmark methods. Biochemical Genetics welcomes articles on the following topics: Genomics; Proteomics; Population genetics; Phylogenetics; Metagenomics; Microbial genetics; Genetics and evolution of wild and cultivated plants; Animal genetics and evolution; Human genetics and evolution; Genetic disorders; Genetic markers of diseases; Gene technology and therapy; Experimental and analytical methods; Statistical and computational methods.
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