Diagnostic Potential of Cross-Specimen microRNA Panels as Biomarkers for Colorectal Cancer: A Systematic Review and Meta-analysis.

IF 4.4 3区 医学 Q1 GENETICS & HEREDITY
Atta Ullah Khan, Maria Ali, Muhammad Aamir Wahab
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引用次数: 0

Abstract

Background and objective: Colorectal cancer remains a major global health challenge, necessitating the development of accurate non-invasive diagnostic tools. Circulating and excretory microRNAs (miRNAs) are promising biomarkers owing to their stability and regulatory roles in tumorigenic pathways. While single miRNA assays often lack sufficient diagnostic accuracy, panels combining multiple miRNAs have shown enhanced performance. This systematic review and meta-analysis evaluated the diagnostic accuracy of multi-miRNA panels and explored their mechanistic relevance to colorectal cancer pathogenesis.

Methods: A comprehensive search of PubMed, Embase, Web of Science, and Scopus was conducted through March 2025 following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The study protocol was registered with PROSPERO (CRD420251060655). Eligible studies assessed the diagnostic accuracy of multi-miRNA panels for colorectal cancer using extractable data on sensitivity, specificity, and area under the curve. Data were extracted independently by two reviewers. A bivariate random-effects model was used to calculate pooled diagnostic estimates. Study quality was assessed with the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool, and heterogeneity was evaluated using I2 statistics. Subgroup analyses were conducted by sample type (e.g., plasma, serum, stool) and panel size. Target genes of recurrent miRNAs were mapped to canonical colorectal cancer-related pathways.

Results: Twenty-nine studies comprising 5497 participants (3070 colorectal cancer cases and 2427 controls) and 35 multi-miRNA panels were included. Pooled sensitivity was 0.85 (95% confidence interval 0.80-0.88), specificity was 0.84 (95% confidence interval 0.80-0.88), and the area under the curve was 0.90, despite substantial heterogeneity (I2 > 77%). Panels derived from plasma samples showed the highest balanced performance (sensitivity 0.88; specificity 0.87), while three-miRNA panels exhibited the best diagnostic trade-offs. Mechanistic analysis of 42 recurrent miRNAs revealed consistent involvement in key colorectal cancer pathways, including PI3K/AKT, Wnt/β-catenin, epithelial-mesenchymal transition, angiogenesis, and immune regulation.

Conclusions: Multi-miRNA panels derived from diverse biospecimen sources demonstrate high diagnostic accuracy for colorectal cancer and are mechanistically linked to fundamental oncogenic pathways. Future efforts should focus on panel standardization, biospecimen-specific validation, and integration into clinical workflows to advance precision oncology.

跨标本microRNA面板作为结直肠癌生物标志物的诊断潜力:系统综述和荟萃分析。
背景和目的:结直肠癌仍然是一个主要的全球健康挑战,需要开发准确的非侵入性诊断工具。循环和排泄microRNAs (miRNAs)由于其稳定性和在肿瘤发生途径中的调节作用而成为有前途的生物标志物。虽然单个miRNA检测通常缺乏足够的诊断准确性,但组合多个miRNA的检测组显示出更高的性能。本系统综述和荟萃分析评估了多mirna面板的诊断准确性,并探讨了它们与结直肠癌发病机制的机制相关性。方法:根据系统评价和元分析指南的首选报告项目,在2025年3月之前对PubMed、Embase、Web of Science和Scopus进行了全面搜索。研究方案已在PROSPERO注册(CRD420251060655)。符合条件的研究使用敏感性、特异性和曲线下面积的可提取数据评估多mirna面板对结直肠癌的诊断准确性。数据由两位审稿人独立提取。采用双变量随机效应模型计算合并诊断估计值。使用诊断准确性研究质量评估2 (QUADAS-2)工具评估研究质量,使用I2统计量评估异质性。按样本类型(如血浆、血清、粪便)和小组大小进行亚组分析。复发性mirna的靶基因被定位到典型的结直肠癌相关途径。结果:29项研究包括5497名参与者(3070名结直肠癌患者和2427名对照组)和35个多mirna小组。合并敏感性为0.85(95%置信区间0.80-0.88),特异性为0.84(95%置信区间0.80-0.88),曲线下面积为0.90,尽管存在很大的异质性(I2 > 77%)。来自血浆样本的小组表现出最高的平衡性能(灵敏度0.88,特异性0.87),而三mirna小组表现出最佳的诊断权衡。42个复发mirna的机制分析显示,它们一致参与结肠直肠癌的关键通路,包括PI3K/AKT、Wnt/β-catenin、上皮-间质转化、血管生成和免疫调节。结论:来自不同生物标本来源的多mirna面板显示出对结直肠癌的高诊断准确性,并且与基本的致癌途径有机制联系。未来的努力应集中在小组标准化、生物标本特异性验证和整合到临床工作流程中,以推进精准肿瘤学。
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
CiteScore
7.80
自引率
2.50%
发文量
53
审稿时长
>12 weeks
期刊介绍: Molecular Diagnosis & Therapy welcomes current opinion articles on emerging or contentious issues, comprehensive narrative reviews, systematic reviews (as outlined by the PRISMA statement), original research articles (including short communications) and letters to the editor. All manuscripts are subject to peer review by international experts.
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