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循环 miRNA 和循环肿瘤 DNA 作为胃癌液体活检标志物的应用。

Circulating miRNA and circulating tumor DNA application as liquid biopsy markers in gastric cancer.

机构信息

School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Tehran, Iran.

Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Tehran, Iran; Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Clin Biochem. 2024 Jul;129:110767. doi: 10.1016/j.clinbiochem.2024.110767. Epub 2024 May 4.

DOI:10.1016/j.clinbiochem.2024.110767
PMID:38705444
Abstract

Liquid biopsy has been investigated as a novel method to overcome the numerous challenges in gastric cancer (GC) management. This non-invasive, feasible, and easy-to-repeat method has been shown to be cost-effective and capable of increasing diagnostic sensitivity and prognostic assessment. Additionally, it is potentially accurate to aid decision-making and personalized treatment planning. MicroRNA (miRNA) and circulating tumor DNA (ctDNA) markers can enhance GC management in various aspects, including diagnosis (mainly earlier diagnosis and the ability to perform population-based screening), prognosis (more precise stratification of prognosis), and treatment (including more accurate prediction of treatment response and earlier detection of resistance to the treatment). Concerning the treatment-related application, miRNAs' mimics and antagonists (by using two main strategies of restoring tumor suppressor miRNAs and inhibiting oncogene miRNAs) have been shown to be effective therapeutic agents. However, these need to be further validated in clinical trials. Furthermore, novel delivery systems, such as lipid-based vectors, polymeric-based vectors, and exosome-based delivery, have been developed to enhance the performance of these agents. Moreover, this paper explores the current detection and measuring methods for these markers. These approaches are categorized into direct methods (e.g., Chem-NAT, HTG EdgeSeq, and Multiplex Circulating Fireplex) and indirect methods (e.g., Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), qPCR, microarray, and NGS) for miRNA detection. For ctDNA measurement, main core technologies like NGS, digital PCR, real-time PCR, and mass spectrometry are suggested.

摘要

液体活检已被研究作为一种新方法来克服胃癌 (GC) 管理中的许多挑战。这种非侵入性、可行且易于重复的方法已被证明具有成本效益,并且能够提高诊断灵敏度和预后评估。此外,它有助于决策和个性化治疗计划,具有潜在的准确性。微小 RNA (miRNA) 和循环肿瘤 DNA (ctDNA) 标志物可以在多个方面增强 GC 的管理,包括诊断(主要是更早的诊断和进行基于人群的筛查的能力)、预后(更精确的预后分层)和治疗(包括更准确地预测治疗反应和更早地检测对治疗的耐药性)。关于治疗相关的应用,miRNA 的模拟物和拮抗剂(通过使用两种主要策略,即恢复肿瘤抑制 miRNA 和抑制癌基因 miRNA)已被证明是有效的治疗剂。然而,这些需要在临床试验中进一步验证。此外,还开发了新型递药系统,如脂质载体、聚合物载体和基于外泌体的递药系统,以增强这些制剂的性能。此外,本文探讨了这些标志物的当前检测和测量方法。这些方法分为直接方法(例如,Chem-NAT、HTG EdgeSeq 和 Multiplex Circulating Fireplex)和间接方法(例如,逆转录定量聚合酶链反应 (RT-qPCR)、qPCR、微阵列和 NGS)用于 miRNA 检测。对于 ctDNA 测量,建议使用 NGS、数字 PCR、实时 PCR 和质谱等主要核心技术。

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