Department of Molecular Biology and Genetics, Tokat Gaziosmanpasa University, 60250, Tokat, Turkey.
Biochem Genet. 2024 Aug;62(4):2721-2742. doi: 10.1007/s10528-023-10577-5. Epub 2023 Nov 24.
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.
胰腺癌(PC)是世界上侵袭性最强和致命性最高的癌症之一,其原因是非特异性的早期临床症状、晚期诊断和较差的生存情况。因此,确定其早期诊断的特异性生物标志物至关重要。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,调节 ANXA2 过表达的机制仍不清楚。已经证实,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,我们通过使用几个生物信息学数据库,重点研究了 ANXA2 的转录谱、甲基化模式、体细胞突变和在 PC 中的预后价值,以探索 ANXA2 的调节机制。我们的结果表明,与正常组织相比,PC 组织中 ANXA2 的表达水平显著增加。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,PC 组织中 ANXA2 启动子的低甲基化可能导致 PC 中 ANXA2 的过表达,但是需要更多的实验研究来证实我们的发现。