Review
Copyright ©The Author(s) 2025.
World J Gastrointest Oncol. Apr 15, 2025; 17(4): 103591
Published online Apr 15, 2025. doi: 10.4251/wjgo.v17.i4.103591
Table 5 Most promising exosomal biomarkers with diagnostic significance in gastrointestinal cancer
GI cancer type
Exosome origin
Candidates’ biomarker
Clinical samples
Supporting evidence
Ref.
Colorectal cancerSerumHsa-circ-0004771179 patients; 45 healthy donorsAUC of 0.86, 0.88 to differentiate stage I/II CRC patients and CRC patients from healthy controls[137]
PlasmaEpcam-CD6359 cancer patients; 20 healthy donorsAUC of 0.96[138]
PlasmaCD147AUC of 0.932, P < 0.001[139]
SerumLncRNA UCA1+, circRNA HIPK3AUC of 0.900, P < 0.0001[140]
PlasmamiR-96-5p and miR-149102 CRC patientsSignificantly decreased in CRC tumor exosomes, and was significantly normalized after surgery[98]
SerummiR-99b-5p and miR-150-5p169 CRC patients, 155 healthy donors, and 20 benign disease patientsThe AUC of miR-99b-5p was 0.628 (32.1% sensitivity and 90.8% specificity), the AUC of miR-150-5p was 0.707 (75.2% sensitivity and 58.8% specificity)[99]
PlasmamiRNA-27a and miRNA-130a 369 peripheral blood samplesThe AUC of miR-27a (miR-130a) was 0.773 (0.742) in the training phase, 0.82 (0.787) in the validation phase[100]
SerummiR-23a and miR-301a12 CRC patients and 8 healthy donorsAUC values for miR-23a and miR-301a were 0.900 and 0.840, respectively[101]
PlasmaLet-7b-3p, miR-139-3p, and miR-145-3p15 colon cancer patients and 10 healthy donorsTheir combination (AUC = 0.927) showed an advantage in identifying CRC patients [102]
SerummiR-126, miR-1290, miR-23a, and miR-940Showed high diagnostic values to differentiate CRC patients at TNM stage I from healthy controls[103]
Esophageal cancerSerummiR-652-5p93 OSCC patients and 93 healthy individualsAUC of 0.901[106]
PlasmamiR-93-5p83 ESCC patients and 83 healthy individualsThe expression level in the plasma of ESCC patients being 1.39 times higher than that of the control population (P = 0.035)[107]
SerummiRNA-182125 ESCC patients and 60 healthy individualsAUC = 0.837, 95%CI: 0.776-0.887[108]
SerumUCA1, POU3F3, ESCCAL-1 and PEG10313 ESCC patients and 313 control individuals without ESCC historyThe AUC for UCA1, POU3F3, ESCCAL-1 and PEG10 were 0.733, 0.717, 0.676, 0.648, respectively[109]
PlasmaNR_039819, NR_036133, NR_003353, ENST00000442416.1, and ENST00000416100.1295 ESCC patients, 43 esophagitis patients, and 49 healthy volunteersThe combined diagnostic value of these five lncRNAs revealed an AUC of 0.9995 (P < 0.001)[110]
CircRNA has-circ-0001946 and has-circ-00436033 pairs of ESCC frozen tumor and non-tumor tissuesThe AUC, sensitivity and specificity of hsa_circ_0001946 was 0.894, 92.80%, of hsa_circ_0043603 was 0.836, 64.92%[111]
Gastric cancerSerumLnc HOTTIP126 GC patients; 120 healthy donorsAUC of 0.827[141]
SerummiR-19b-3p and miR-106a-5p130 GC patients and 130 healthy donorsLevels of exosomes of patients with GC were markedly overexpressed compared to healthy donors[114]
SerummiR10b-5p, miR132-3p, miR185-5p, miR195-5p, miR-20a3p, and miR296-5pThe training (49 gastric cancer vs 47 NCs) and validation phases (154 gastric cancer vs 120 NCs)AUC were 0.764 and 0.702 for the training and validation phases, respectively[115]
SerummiR-10a-5p, miR-19b-3p, miR-215-5p, and miR-18a-5pA pair of 43 primary adenocarcinoma GC tissue samples with corresponding adjacent non-malignant counterpartsAUC of 0.801, 0.721, 0.780 and 0.736, respectively[116]
SerumLncRNA PCSK2-2:129 healthy people and 63 gastric cancer patientsAUC of 0.896[117]
PlasmaLncRNA SLC2A12-10:160 GC patients and 60 age-matched healthy controlsThe area under the ROC curve was 0.776[118]
PlasmaLncUEGC1 and lncUEGC2Five healthy individuals and ten stages I GC patients and from culture media of four human primary stomach epithelial cells and four GCCsLncUEGC1 exhibited AUC values of 0.8760 and 0.8406 in discriminating EGC patients from healthy individuals[119]
PlasmaHsa_circ_0065149Low expression levels in GC tissues were significantly associated with the tumor diameter (P = 0.034) and perineural invasion (P = 0.037)[120]
SerumCircSHKBP172 paired GC tissues and normal tissuesThe expression of circSHKBP1 was 2.31-fold higher in GC tissues on average than in normal tissues[121]
SerummiR-15b-3p108 GC patients; 108 healthy donorsAUC of 0.820; specificity of 80.6%; sensitivity of 74.1%[142]
Hepatocellular and biliary cancerPlasmaAFP; GPC3; ALB; APOH; FABP1; FGB; FGG; AHSG; RBP4; TF mRNA36 HCC patients; 26 cirrhosisAUC of 0.87; sensitivity of 93.8%; specificity of 74.5%[143]
SerummiR-21Higher in HCC patients[144]
SerumCEA; GPC-3, and PD-L112 HCC patients; 12 hepatitis B; 6 healthy donorsHigher in HCC patients[74]
PlasmamiRNA-122, miRNA-21, and miRNA-9650 patients with HCC and 50 patients with hepatic cirrhosis and 50 healthy volunteersAUC of 0.924; 95%CI; sensitivity 82%, specificity 92% to discriminating HCC from the cirrhosis group[123]
SerummiR-10b-5p28 healthy individuals, 60 with chronic liver disease, and 90 with HCCAUC of 0.934[124]
PlasmamiR-21-5p and miR-92a-3p20 healthy individuals, 38 with liver cirrhosis, and 48 with HCCMiR-21-5p was up-regulated and miR-92a-3p was down-regulated, and after incorporating AFP, the AUC was 0.85[125]
SerummiR-4661-5p15 normal subjects, 20 with CH, 10 with LC, 18 with HCC (Edmonson grade 1), and 45 with moderate to poorly differentiated HCCAUC of 0.917 diagnose HCC in all stages, AUC of 0.923 in early stage[126]
PlasmaRN7SL1, SNHG1, ZFAS1, and LINC0135957 plasma cell-free RNA transcriptome and 20 exosomal RNA transcriptomesRN7SL1 discriminated HCC samples from negative controls (AUC = 0.87; 95%CI: 0.817-0.920)[127]
PlasmamiR-96-5p, miR-151a-5p, miR-191-5p, and miR-4732-3p5 CCA patients and 4 GBC patients before and after surgery, 40 healthy individuals, 45 more CCA patients and 24 more GBC patients to validateAUC of 0.733, 0.7639, 0.5417, and 0.6544, respectively[128]
Pancreatic cancerPlasmamiRNA-10b3 PDAC patients; 3 CP patients; 3 healthy donorsHigher in PDAC patients[145]
PlasmamiRNA-10bPDAC patients; CP patients and healthy donorsHigher in PDAC patients[146]
Mouse plasma samplesmiR-3970-5p9 healthy donors; 9 pancreatic intraepithelial neoplasia patients; 9 PDAC patientsAccuracy of 65%[147]
SerumEpCAM, Glypican190% accuracy for pancreatic cancer or normal pancreatic epithelial cell lines; 87 and 90% predictive accuracy for healthy control and EPC individual samples[148]
PlasmamiR-4525, miR-451a and miR-2155 patients with PDAC and 20 healthy volunteersThe exosomal levels from PDAC patients were significantly higher than those from healthy volunteers[130]
SerummiR-1246, miR-4306, and miR-4644131 pancreatic cancer patients and 89 controlsSignificantly increased in 83% of pancreatic cancer patients compared to healthy controls, P < 0.05[131]
PlasmaLINC01268, LINC02802, AC124854.1, AL132657.178 pancreatic cancer patients and 70 healthy controlsThe ROC analysis revealed AUC values of 0.8421, 0.6544, 0.7190, and 0.6231 for LINC01268, LINC02802, AC124854.1, and AL132657.1, respectively[132]
PlasmaLong-stranded RNAs (FGA, KRT19, HIST1H2BK, ITIH2, MARCH2, CLDN1, MAL2 and TIMP1)Samples from 284 patients with PDAC, 100 patients with chronic pancreatitis and 117 healthy controlsDiagnosed PDAC with 0.949 AUC to identify stage I/II tumors[133]
SerumSmall nucleolar RNAs: WASF2, ARF6, SNORA74A, and SNORA2527 pancreatic cancer patients and 13 controlsThe AUCs of WASF2, ARF6, SNORA74A, and SNORA25 in serum from patients in the early stages of pancreatic cancer (stages 0, I, and IIA) were > 0.9[134]
SerumGlypican1190 pancreatic cancer patients and 131 controlsSensitivity of 100%; specificity of 100%; positive predictive value of 100%; negative predictive value of 100%; AUC of 1.0[135]