揭示PDAC中差异DNA甲基化的临床影响：一项系统综述

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer Pub Date : 2025-03-23 DOI:10.1016/j.ejca.2025.115384

Julia Adriana Kasmirski, Raj Roy, Christopher Wu, Lauren Wheeler, K. Kerrick Akinola, Herbert Chen, J. Bart Rose, Changde Cheng, Smita Bhatia, Andrea Gillis

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引用次数: 0

摘要

尽管在改善临床结果方面做出了重大努力，但胰腺导管腺癌（PDAC）的死亡率很高。与该病相关的不良预后是多因素的，并与与其发病机制相关的高度可变的遗传谱相关。包括DNA甲基化在内的表观遗传修饰进一步影响遗传物质的表达。然而，对DNA甲基化在PDAC中的临床影响还没有全面的了解。方法在国际前瞻性系统评价数据库（CRD42023451955）上注册了一篇系统文献综述，并遵循系统评价和荟萃分析首选报告项目（PRISMA）指南。使用以下数据库进行电子检索：CINAHL Plus、Cochrane Library、Embase、Web of Science、Ovid Medline和谷歌Scholar。纳入标准包括PDAC诊断患者的研究，以及可能影响PDAC诊断、预后或生存的基因或CpG位点的信息。结果初步检索到2402篇文献，排除重复文献423篇。应用排除标准后，纳入了19项研究。最常见的影响肿瘤发病的基因为SFRP1 （n = 3/ 19,15.7 %）和NPTX2 （n = 2/ 19,10,5 %）。研究表明，SFRP1和NPTX2的高甲基化与不良预后相关。结论spdac与一系列表观遗传修饰有关。与PDAC相关的特定基因的甲基化可能影响患者的生存和预后，是一种治疗靶点。个体患者表观遗传分析可能是指导PDAC治疗和预后的未来方向。

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Unraveling the clinical impact of differential DNA methylation in PDAC: A systematic review

Introduction

Despite significant efforts to improve clinical outcomes, pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate. The poor prognosis associated with this disease is multifactorial and associated with a highly variable genetic profile associated with its pathogenesis. Epigenetic modifications including DNA methylation further affect the expression of genetic material. However, there is no comprehensive understanding of the clinical impact of DNA methylation in PDAC.

Methods

A systematic literature review was registered on the International Prospective Register of Systematic Reviews database (CRD42023451955) and followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. An electronic search was conducted using the following databases: CINAHL Plus, Cochrane Library, Embase, Web of Science, Ovid Medline, and Google Scholar. Inclusion criteria included studies of patients with a PDAC diagnosis and information regarding genes or CpG sites that potentially affect diagnosis, prognosis, or survival of PDAC.

Results

The initial search retrieved 2402 articles, and 423 duplicates were excluded. After exclusion criteria was applied, 19 studies were included. The most common genes recorded as affecting tumor pathogenesis were SFRP1 (n = 3/19, 15.7 %) and NPTX2 (n = 2/19, 10,5 %). Studies indicated that hypermethylation of SFRP1 and NPTX2 were associated with poor prognosis.

Conclusions

PDAC is associated with a range of epigenetic modifications. Methylation of specific genes related to PDAC may influence survival and prognosis and be a therapeutic target. Individual patient epigenetic analysis may be a future direction in directing PDAC treatment and prognosis.

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来源期刊

European Journal of Cancer 医学-肿瘤学

CiteScore

11.50

自引率

4.80%

发文量

953

审稿时长

23 days

期刊介绍： The European Journal of Cancer (EJC) serves as a comprehensive platform integrating preclinical, digital, translational, and clinical research across the spectrum of cancer. From epidemiology, carcinogenesis, and biology to groundbreaking innovations in cancer treatment and patient care, the journal covers a wide array of topics. We publish original research, reviews, previews, editorial comments, and correspondence, fostering dialogue and advancement in the fight against cancer. Join us in our mission to drive progress and improve outcomes in cancer research and patient care.