Ziranu Pina, Pretta Andrea, Saba Giorgio, Spanu Dario, Donisi Clelia, Ferrari Paolo Albino, Cau Flaviana, D'Agata Alessandra Pia, Piras Monica, Mariani Stefano, Puzzoni Marco, Pusceddu Valeria, Coghe Ferdinando, Faa Gavino, Scartozzi Mario
Medical Oncology Unit, University Hospital and University of Cagliari, 09042 Cagliari, Italy.
Division of Thoracic Surgery, Azienda di Rilievo Nazionale ed Alta Specializzazione "G. Brotzu", 09121 Cagliari, Italy.
Int J Mol Sci. 2025 Aug 6;26(15):7619. doi: 10.3390/ijms26157619.
Liquid biopsy has emerged as a valuable tool for the detection and monitoring of colorectal cancer (CRC), providing minimally invasive insights into tumor biology through circulating biomarkers such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Additional biomarkers, including tumor-educated platelets (TEPs) and exosomal RNAs, offer further potential for early detection and prognostic role, although ongoing clinical validation is still needed. This review summarizes the current evidence on the diagnostic, prognostic, and predictive capabilities of liquid biopsy in both metastatic and non-metastatic CRC. In the non-metastatic setting, liquid biopsy is gaining traction in early detection through screening and in identifying minimal residual disease (MRD), potentially guiding adjuvant treatment and reducing overtreatment. In contrast, liquid biopsy is more established in metastatic CRC for monitoring treatment responses, clonal evolution, and mechanisms of resistance. The integration of ctDNA-guided treatment algorithms into clinical practice could optimize therapeutic strategies and minimize unnecessary interventions. Despite promising advances, challenges remain in assay standardization, early-stage sensitivity, and the integration of multi-omic data for comprehensive tumor profiling. Future efforts should focus on enhancing the sensitivity of liquid biopsy platforms, validating emerging biomarkers, and expanding multi-omic approaches to support more targeted and personalized treatment strategies across CRC stages.
液体活检已成为检测和监测结直肠癌（CRC）的一种有价值的工具，通过循环生物标志物，如循环肿瘤DNA（ctDNA）、循环肿瘤细胞（CTC）、微小RNA（miRNA）、长链非编码RNA（lncRNA）和环状RNA（circRNA），对肿瘤生物学提供微创性的见解。其他生物标志物，包括肿瘤诱导血小板（TEP）和外泌体RNA，为早期检测和预后作用提供了进一步的潜力，尽管仍需要进行临床验证。本综述总结了目前关于液体活检在转移性和非转移性CRC中的诊断、预后和预测能力的证据。在非转移性情况下，液体活检在通过筛查进行早期检测和识别微小残留病（MRD）方面越来越受到关注，有可能指导辅助治疗并减少过度治疗。相比之下，液体活检在转移性CRC中用于监测治疗反应、克隆进化和耐药机制方面更为成熟。将ctDNA指导的治疗算法整合到临床实践中可以优化治疗策略并减少不必要的干预。尽管取得了有前景的进展，但在检测标准化、早期敏感性以及整合多组学数据以进行全面的肿瘤分析方面仍然存在挑战。未来的努力应集中在提高液体活检平台的敏感性、验证新兴生物标志物以及扩展多组学方法，以支持跨CRC各阶段更具针对性和个性化的治疗策略。
