Shweikeh Faris, Zeng Yuhao, Jabir Abdur Rahman, Whittenberger Erica, Kadatane Saurav P, Huang Yuting, Mouchli Mohamad, Castillo Dani Ran
Department of Internal Medicine, Cleveland Clinic Akron General, OH, USA.
Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Cancer Treat Res Commun. 2024;42:100872. doi: 10.1016/j.ctarc.2025.100872. Epub 2025 Jan 26.
Colorectal cancer (CRC), the third most commonly diagnosed and second most lethal cancer worldwide, necessitates efficient early detection strategies to improve patient outcomes. This review evaluates the promise of novel blood-based biomarkers for early detection of CRC.
A systematic review, registered with PROSPERO (CRD42024513770) and adhering to PRISMA guidelines, was conducted across multiple databases from January 1st, 2020 to December 31st, 2022. The comprehensive search strategy centered on sensitivity, specificity, and AUC-ROC of multiple types of molecular blood biomarkers.
Of total of 142 included articles, 59 were on protein, 58 on RNA, and 21 on DNA. The investigation into DNA biomarkers revealed that cfDNA and ctDNA carry significant potential for early CRC diagnosis. For instance, methylation patterns in genes such as MYO1-G and NDRG4 exhibited high diagnostic accuracies with AUCs reaching up to 0.996. RNA biomarkers like miRNAs and circRNAs also showed promising results, with circ_0011536 achieving AUCs of 0.982. Protein biomarkers, contrasted with established cancer markers, unveiled notable candidates like Irisin and ANXA2, with AUCs surpassing 0.96. The review highlights several individual markers and panels with the potential to improve upon existing CRC screening tests.
Despite the promise shown by the novel biomarkers, challenges persist, including small sample sizes, potential selection biases, and a lack of comprehensive cost-effectiveness analysis. Future research should focus on large-scale, multicenter, prospective studies across diverse populations. The findings advocate for an integrated biomarker approach, potentially revolutionizing CRC screening and aligning it with clinical realities through rigorous validation.
结直肠癌（CRC）是全球第三大常见诊断癌症和第二大致命癌症，需要有效的早期检测策略来改善患者预后。本综述评估了新型血液生物标志物用于早期检测CRC的前景。
进行了一项系统综述，在PROSPERO（CRD42024513770）注册并遵循PRISMA指南，于2020年1月1日至2022年12月31日在多个数据库中开展。全面的检索策略围绕多种类型分子血液生物标志物的敏感性、特异性和AUC-ROC展开。
在总共纳入的142篇文章中，59篇关于蛋白质，58篇关于RNA，21篇关于DNA。对DNA生物标志物的研究表明，cfDNA和ctDNA在早期CRC诊断中具有巨大潜力。例如，MYO1-G和NDRG4等基因的甲基化模式显示出高诊断准确性，AUC高达0.996。miRNAs和circRNAs等RNA生物标志物也显示出有前景的结果，circ_0011536的AUC达到0.982。与既定癌症标志物相比，蛋白质生物标志物揭示了Irisin和ANXA2等显著候选物，AUC超过0.96。该综述突出了几个有潜力改进现有CRC筛查测试的单个标志物和组合。
尽管新型生物标志物显示出前景，但挑战依然存在，包括样本量小、潜在的选择偏倚以及缺乏全面的成本效益分析。未来研究应专注于跨不同人群的大规模、多中心、前瞻性研究。研究结果提倡采用综合生物标志物方法，可能会彻底改变CRC筛查并通过严格验证使其与临床实际情况相契合。
