Liquid biopsies in colorectal cancer screening and diagnosis

Table 1 Comparison of exosomal biomarkers for colorectal cancer diagnosis

Ref.	Biomarkers	Expression in CRC vs controls	Diagnostic performance (sensitivity/specificity/AUC)	Study size (CRC patients/HCs)	Validation status and key findings
Li et al[80], 2023	Exosomal miR-548am-5p	Upregulated	Not mentioned	Clinical tissues: 18 pairs of CRC and adjacent nontumor tissues	This study elucidates the oncogenic function of exosomal miR-548am-5p rather than establishing its clinical diagnostic value
Ogata-Kawata et al[81], 2014	Seven-miRNA Panel (e.g., let-7a, miR-1246, miR-23a)	Upregulated	Reported high sensitivity in ROC analysis. Specific AUC for the panel is not provided in the excerpt, but individual miRNAs like miR-1246 showed high diagnostic accuracy	Discovery: 88 CRC/11 HC; validation: 13 CRC	Preliminary validation in an independent set; miRNA levels decreased post-surgery, indicating tumor origin; the study provides early but promising evidence
Zhao et al[83], 2025	miR-205-5p	Downregulated	AUC for CRC vs HC: 0.873	157 CRC/135 HC/20 benign	Single-cohort study with a relatively large sample; expression was lower in CRC and early-stage patients, and increased postoperatively. Shows potential as a diagnostic biomarker
Wang et al[84], 2022	miR-377-3p and miR-381-3p	Downregulated	Combined (CRC vs HC): AUC = 0.886miR-377-3p: AUC = 0.826; miR-381-3p: AUC = 0.843	175 CRC/172 HC	Single-cohort study; the combination showed improved diagnostic performance; expression was downregulated in early-stage CRC
Han et al[85], 2021	Panel: MiR-15b, miR-16, miR-21, miR-31	Upregulated	CRC vs HC: Sensitivity: 95.06%, specificity: 94.44% CRC vs Adenoma: Sensitivity: 85.19%, specificity: 82.09%	Training: 123 CRC/150 HC; validation: 81 CRC/90 HC	Validated in an independent cohort; the panel demonstrated high and consistent diagnostic accuracy in both training and validation sets
Hu et al[86], 2018	Six exosomal lncRNAs (e.g., LNCV6_116109)	Upregulated	Individual AUCs ranged from 0.650 to 0.770	50 CRC/50 HC	Proof-of-concept study; provides preliminary AUC values for individual lncRNAs, suggesting their potential as noninvasive biomarkers; requires further validation
Du et al[87], 2022	Panel: MiR-654-5p, miR-126, miR-10b, miR-144	miR-654-5p, -126, -10b upregulated; miR-144 downregulated	The diagnostic model based on this 4-miRNA signature achieved an AUC of 0.913 in the clinical validation cohort	88 CRC/11 HCclinical; validation: 100 CRC/120 HC	Validated in an independent clinical cohort; the signature was identified via machine learning and showed high diagnostic potential in validation
Zhang et al[88], 2024	miR-99b-5p and miR-409-3p[88]	Upregulated	For early CRC: miR-99b-5p alone: AUC = 0.735, sensitivity: 72.7%, specificity: 78.3%miR-99b-5p + miR-409-3p: AUC = 0.741, sensitivity: 77.3%, specificity: 78.3% + CEA: AUC = 0.812, sensitivity: 90.9%, specificity: 65.2%	68 CRC/27 HC	Single-cohort study; the study highlights the value of combining exosomal miRNAs with the traditional protein marker CEA to significantly boost sensitivity for early CRC detection

CRC: Colorectal cancer; AUC: Area under the curve; HC: Healthy control; ROC: Receiver operating characteristic; CEA: Carcinoembryonic antigen; miRNA: Micro RNA.