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利用胰腺导管腺癌中的表观遗传改变用于临床应用。

Leveraging epigenetic alterations in pancreatic ductal adenocarcinoma for clinical applications.

作者信息

Tost Jorg, Ak-Aksoy Secil, Campa Daniele, Corradi Chiara, Farinella Riccardo, Ibáñez-Costa Alejandro, Dubrot Juan, Earl Julie, Melian Emma Barreto, Kataki Agapi, Kolnikova Georgina, Madjarov Gjorgji, Chaushevska Marija, Strnadel Jan, Tanić Miljana, Tomas Miroslav, Dubovan Peter, Urbanova Maria, Buocikova Verona, Smolkova Bozena

机构信息

Centre National de Recherche en Génomique Humaine, CEA - Institut de Biologie François Jacob, University Paris - Saclay, Evry, France.

Bursa Uludag University Faculty of Medicine, Medical Microbiology, Bursa 16059, Turkey.

出版信息

Semin Cancer Biol. 2025 Feb;109:101-124. doi: 10.1016/j.semcancer.2025.01.003. Epub 2025 Jan 23.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by late detection and poor prognosis. Recent research highlights the pivotal role of epigenetic alterations in driving PDAC development and progression. These changes, in conjunction with genetic mutations, contribute to the intricate molecular landscape of the disease. Specific modifications in DNA methylation, histone marks, and non-coding RNAs are emerging as robust predictors of disease progression and patient survival, offering the potential for more precise prognostic tools compared to conventional clinical staging. Moreover, the detection of epigenetic alterations in blood and other non-invasive samples holds promise for earlier diagnosis and improved management of PDAC. This review comprehensively summarises current epigenetic research in PDAC and identifies persisting challenges. These include the complex nature of epigenetic profiles, tumour heterogeneity, limited access to early-stage samples, and the need for highly sensitive liquid biopsy technologies. Addressing these challenges requires the standardisation of methodologies, integration of multi-omics data, and leveraging advanced computational tools such as machine learning and artificial intelligence. While resource-intensive, these efforts are essential for unravelling the functional consequences of epigenetic changes and translating this knowledge into clinical applications. By overcoming these hurdles, epigenetic research has the potential to revolutionise the management of PDAC and improve patient outcomes.

摘要

胰腺导管腺癌(PDAC)是一种侵袭性很强的恶性肿瘤,其特点是发现晚、预后差。最近的研究突出了表观遗传改变在推动PDAC发生发展中的关键作用。这些变化与基因突变共同促成了该疾病复杂的分子格局。DNA甲基化、组蛋白标记和非编码RNA的特定修饰正成为疾病进展和患者生存的有力预测指标,与传统临床分期相比,有望提供更精确的预后工具。此外,在血液和其他非侵入性样本中检测表观遗传改变有望实现PDAC的早期诊断和更好的管理。本综述全面总结了目前PDAC表观遗传学研究的情况,并指出了仍然存在的挑战。这些挑战包括表观遗传图谱的复杂性、肿瘤异质性、获取早期样本的机会有限以及对高灵敏度液体活检技术的需求。应对这些挑战需要方法的标准化、多组学数据的整合以及利用机器学习和人工智能等先进的计算工具。尽管这些工作资源密集,但对于阐明表观遗传变化的功能后果并将这些知识转化为临床应用至关重要。通过克服这些障碍,表观遗传学研究有可能彻底改变PDAC的管理方式并改善患者预后。

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