关键词: ANXA2 Bioinformatics Epigenetics Hypomethylation Pancreatic cancer

Mesh : Annexin A2 / genetics metabolism Humans Pancreatic Neoplasms / genetics metabolism pathology Prognosis Promoter Regions, Genetic DNA Methylation Gene Expression Regulation, Neoplastic Up-Regulation Biomarkers, Tumor / genetics metabolism

来  源:   DOI:10.1007/s10528-023-10577-5

Abstract:
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.
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,可怜的生存。因此,确定特异性生物标志物对其早期诊断至关重要.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。使其成为新兴的生物标志物和潜在的癌症治疗靶点。然而,ANXA2过表达的调节机制尚不清楚.众所周知,遗传和表观遗传改变可能导致基因表达的广泛失调。因此,在这项研究中,我们通过研究ANXA2的转录谱,重点探索ANXA2的调控机制,甲基化模式,体细胞突变,使用几个生物信息学数据库,ANXA2在PC中的预后价值。我们的结果表明,与正常组织相比,PC组织中ANXA2的表达水平显着增加。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,ANXA2启动子在PC组织中低甲基化,这可能导致PC中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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