Diagnostic value of genetic and epigenetic biomarker panels for colorectal cancer detection: a systematic review.

IF 2.5 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

International Journal of Colorectal Disease Pub Date : 2025-05-22 DOI:10.1007/s00384-025-04904-y

Georgios Alampritis, Sarah Nohelia Thoukididou, Maria Ramos, Pantelis Georgiou, Melpomeni Kalofonou, Constantinos Simillis

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引用次数: 0

Abstract

Purpose: Exploration of effective screening methods is imperative to improve current screening for colorectal cancer (CRC). Our aim was to systematically search the literature to identify and assess the diagnostic accuracy of both genetic and epigenetic biomarker panels for CRC detection using liquid biopsies for circulating tumour DNA (ctDNA) from stool, blood, or urine.

Methods: A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) with searches in Medline, Embase, CENTRAL, and Web Of Science from inception up to March 20, 2025, using pre-defined keywords. Study quality assessment was performed using QUADAS-2 tool (Quality Assessment for Diagnostic Accuracy Studies 2). Primary and secondary outcomes were panel performance (sensitivity and specificity) for CRC, advanced precancerous lesions (APL), and staging of disease.

Results: Forty-four studies were included. Exceptional performance for both CRC (sensitivity and specificity) and APL (sensitivity) was displayed by biomarker panels including methylated SDC2 with methylated SFRP1/2 (CRC: 91.5%/97.3%, APL: 89.2%) or methylated TFPI2 (CRC: 94.9%/98.1%, APL: 100%), and a 5-biomarker panel of mutational targets APC, Bat-26, KRAS, L-DNA, and p53 (CRC: 91.0%/93.0%, APL: 82.0%). Suboptimal APL sensitivities up to 57.0% were exhibited by Cologuard and variant panels (including KRAS, methylated BMP3, methylated NDRG4, FIT), and 47.8% for combinations including methylated SEPT9.

Conclusions: High-performance, candidate ctDNA biomarker panels with exceptional diagnostic accuracy for both CRC and APL have been identified. Further work should focus on the development of large-scale studies to justify their clinical implementation.

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遗传和表观遗传生物标志物面板在结直肠癌检测中的诊断价值：系统综述。

目的：探索有效的筛查方法是提高现行结直肠癌筛查水平的必要条件。我们的目的是系统地检索文献，以确定和评估使用粪便、血液或尿液中循环肿瘤DNA （ctDNA）液体活检检测CRC的遗传和表观遗传生物标志物小组的诊断准确性。方法：根据系统评价和荟萃分析的首选报告项目（PRISMA），使用预定义的关键词在Medline， Embase， CENTRAL和Web Of Science中搜索，从成立到2025年3月20日进行系统评价。使用QUADAS-2工具（诊断准确性研究质量评估2）进行研究质量评估。主要和次要结局是CRC、晚期癌前病变（APL）和疾病分期的整体表现（敏感性和特异性）。结果：纳入44项研究。通过包括SDC2甲基化和SFRP1/2甲基化（CRC: 91.5%/97.3%, APL: 89.2%）或TFPI2甲基化（CRC: 94.9%/98.1%, APL: 100%）以及5个生物标志物突变靶APC、Bat-26、KRAS、L-DNA和p53 （CRC: 91.0%/93.0%, APL: 82.0%）在内的生物标志物小组，CRC（敏感性和特异性）和APL（敏感性）都表现出了卓越的表现。colcolguard和变异组（包括KRAS、甲基化BMP3、甲基化NDRG4、FIT）的APL敏感性为57.0%，而包括甲基化SEPT9的组合的APL敏感性为47.8%。结论：已经确定了对结直肠癌和APL具有卓越诊断准确性的高性能候选ctDNA生物标志物面板。进一步的工作应侧重于开展大规模研究，以证明其临床应用的合理性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Colorectal Disease 医学-外科

CiteScore

4.90

自引率

3.60%

发文量

206

审稿时长

3-8 weeks

期刊介绍： The International Journal of Colorectal Disease, Clinical and Molecular Gastroenterology and Surgery aims to publish novel and state-of-the-art papers which deal with the physiology and pathophysiology of diseases involving the entire gastrointestinal tract. In addition to original research articles, the following categories will be included: reviews (usually commissioned but may also be submitted), case reports, letters to the editor, and protocols on clinical studies. The journal offers its readers an interdisciplinary forum for clinical science and molecular research related to gastrointestinal disease.