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©The Author(s) 2022.
World J Gastroenterol. Apr 21, 2022; 28(15): 1508-1525
Published online Apr 21, 2022. doi: 10.3748/wjg.v28.i15.1508
Published online Apr 21, 2022. doi: 10.3748/wjg.v28.i15.1508
Table 1 The role of microRNAs as diagnostic and prognostic biomarkers in cholangiocarcinoma
Circulating microRNA | Biofluid | Comparison | Statistics | Discriminant specificity | Valuable considerations | Subjective rating |
miR-21 | Increased in serum[27,28]; plasma[34]; urine[35] | iCC (n = 74), HC (n = 74)[27]; CCA (n = 11), HC (n = 9)[28]. iCC (n = 25), HC (n = 7); CCA (n = 22), HC (n = 21) | AUROC vs HC: Serum: 0.91[27]; serum: 0.80[28]; plasma 0.94[34]. Combined miR-21 + miR 192. Urine: 0.85[35] | LOW. Also increased in HCC[36] and other malignancies[37,38] | Corelates well with tumor stage and survival[39]. Most data support | Useful |
miR-150-5p | Decreased in serum and bile[40] | CCA (n = 28), PSC (n = 30), HC (n = 50) | Significantly decreased vs HC and PSC[40] association with | LOW. Upregulation suppresses tumor progression in colorectal cancer[41] | Appears to correlate with tumor staging. Added value of the CA19-9 combination. Contradictory findings: Report of being upregulated in iCCA (AUROC: 0.76)[27] | Debatable |
miR-26a | Increased in serum[29] | CCA (n = 66), HC (n = 66) | AUROC vs HC: 0.90[29] | Moderate involved in HCC[30] | Correlates well with tumor stage, metastases, differentiation, and survival. Reliable decrease following curative surgery[29] | Promising |
miR-30d-5p | Increased in bile[31] | CCA (n = 48), benign BTD (n = 58) | AUROC vs benign biliary obstruction 0.730[31] | Moderate downregulated in gastric cancer[32] | Increased sensitivity and specificity compared to CA19-9 | Debatable |
miR-222; miR-483-5p | Increased in serum[33] | CCA (n = 70), PSC (n = 70), HC (n = 70) | AUROC vs PSC; miR-222: 0.71; miR-483-5p: 0.70 combined miR-222 and 483-5p: 0.74[33] | No evidence of overlap with other cancers | Might be useful for monitoring patients with PSC | Promising |
Table 2 Proteins associated with favorable cholangiocarcinoma diagnostic potential
Protein | Comparison | SEN (%) | SPE (%) | AUC | Ref. |
Tissue | |||||
CYFRA 21-1 | iCCA (n = 217) vs HC (n = 514) meta-analysis | 81.0 | 86.0 | 0.904 | [58] |
DKK1 | iCCA (n = 37) vs HC (n = 50) | 75.7 | 100.0 | 0.872 | [52] |
DKK1 + CA19-9 | iCCA(n = 79) vs HC (n = 160) | 74.7 | 56.3 | 0.793 | [60] |
IL-6 | CCA (n = 26), HCC (n = 26) and HC (n = 23) | 73.0 | 92.0 | 0.875 | [53] |
MMP-7 | CCA (n = 44) vs benign BTD (n = 36) | 76.3 | 46.8 | 0.730 | [56] |
CCA (n = 59) vs benign BTD (n = 128) | 75.0 | 78.0 | 0.840 | [57] | |
MUC5AC | CCA (n = 49), benign BTD (n = 23), HC (n = 16) | 71.0 | 94.7 | 0.909 | [55] |
OPN | CCA (n = 107) vs HC (n = 55) | 87.5 | 100.0 | 0.964 | [50] |
S100A6 | CCA (n = 112) vs HC (n = 42) | 86.2 | 90.9 | 0.909 | [51] |
SSP411 | CCA (n = 30), benign BTD (n = 13) and HC (n = 23) | 90.0 | 83.3 | 0.913 | [54] |
TGF-β1 | CCA (n = 45), other disease conditions related inflammation (n = 25) and HC (n = 45) | 71.1 | 68.9 | 0.668 | [78] |
TSP-2 + CA19-9 | dCCA (n = 51), pancreatic ductal adenocarcinoma (n = 52), benign pancreatic diseases (n = 27) and HC (n = 52) | 79.0 | 96.0 | 0.920 | [61] |
uPAR | CCA (n = 118), and HC (n = 76) | 95.3 | 89.7 | 0.969 | [59] |
Biomarker panel: S100A9, MUC5AC, TGF-β1, Ang-2, and CA19-9 | CCA (n = 40), non-CCA (n = 40) and HC (n = 40) | 95.0 | 90.0 | 0.975 | [62] |
Table 3 Proteins associated with poor outcome in cholangiocarcinoma patients
Protein | Comparison | Outcome | Ref. |
Tissue | |||
CDH17 | CCA (n = 180) | High CDH17 was associated with a worse OS and recurrence-free survival | [64] |
HHLA2 | iCCA (n = 218) meta-analysis | High HHLA2 expression was significantly associated with shorter OS | [74] |
KL-6 | CCA (n = 21), cHCC-CCA (n = 12), HCC (n = 78) | A key molecule for tumor cell adhesion and invasion | [63] |
KLK11 | CCA and adjacent normal tissues (n = 18) | OS of CCA patients with a high expression of KLK11 was significantly shorter than those with a low expression of KLK11 (414 d vs 809 d, respectively; P = 0.048) | [65] |
LC3 | cHCC-CC (n = 40) | The 5-yr OS and disease-free survival rates were 61.2% and 74.6% in high LC3 expression patients and 0% and 0% in those with low LC3 expression | [70] |
MMP-7 | Perihilar iCCA, hCCA, and eCCA (n = 66) | Patients with moderate to marked expression of MMP-7 had a significantly poorer prognosis, as compared to those with negative to focal expression | [72] |
iCCA (n = 35) | The 5-yr survival rates of MMP-7(+) and MMP-7(−) patients were 72.7% and 18.3%, respectively | [73] | |
PD-L1 | CCA (n = 2012) meta-analysis | Overexpression of PD-L1 was significantly associated with worse OS | [17] |
S100P | CCA (n = 1925) meta-analysis | S100 calcium binding protein P overexpression was associated with poor OS | [69] |
uPa | iCCA (n = 174) | High uPa expression was correlated with lymphatic invasion and metastasis of CCA patients | [71] |
uPAR | CCA (n = 108) vs normal tissue (n = 108) | The median OS was 890 d for patients with uPAR positive vs 1.321 d for patients with uPAR negative | [59] |
Biomarker panel: CEA, AFP, and Ki67 | iCCA (n = 92) | higher AFP, CEA, and Ki67, as well as more advanced TNM staging were associated with worse OS | [75] |
Serum | |||
CIAPIN1 | CCA (n = 159) vs HC (n = 93) | Higher CIAPIN1 level was significantly associated with shorter OS time | [66] |
DKK1 + CA19-9 | iCCA (n = 79) vs HC (n = 160) | DKK-1 in combination with CA19-9 showed a better diagnostic performance than CA19-9 alone; low DKK-1 and CA19-9 were associated with longer OS | [60] |
MUC5AC | CCA (n = 49), benign BTD (n = 23), HC (n = 16) | High MUC5AC level was related to a worse prognosis compared with patients with lower levels, with 3-yr survival rates of 21.5% and 59.3%, respectively | [55] |
OPN | CCA (n = 107) vs HC (n = 55) | Poor postoperative survival | [50] |
OPN/tumor volume | iCCA (n = 124) | Low circulating OPN per tumor volume was associated with shorter OS and disease-free survival | [77] |
PD-L1 | CCA (n = 73) vs HC (n = 42) | Low PD-L1 levels displayed a strong trend towards an impaired prognosis | [76] |
S100A6 | CCA (n = 112) vs HC (n = 42) | S100A6 potential was like those of the clinically established biomarkers CEA and CA19-9 | [67] |
uPAR | CCA (n = 168) | Baseline level of uPAR was an independent predictor of survival; a high level of uPAR after 2 cycles of chemotherapy was associated with poor survival | [68] |
CCA (n = 117), HC (n = 76) | Multivariate Cox-regression analysis revealed circulating uPAR levels as an independent prognostic marker following biliary tract cancer resection | [59] | |
Biomarker panel: S100A9, MUC5AC, TGF-β1, Ang-2, and CA19-9 | CCA (n = 40), and non-CCA patients (n = 40) and HC (n = 40) | TGF-β1 and Ang-2 are predictors of higher TNM stages | [62] |
- Citation: Mocan LP, Ilieș M, Melincovici CS, Spârchez M, Crăciun R, Nenu I, Horhat A, Tefas C, Spârchez Z, Iuga CA, Mocan T, Mihu CM. Novel approaches in search for biomarkers of cholangiocarcinoma. World J Gastroenterol 2022; 28(15): 1508-1525
- URL: https://www.wjgnet.com/1007-9327/full/v28/i15/1508.htm
- DOI: https://dx.doi.org/10.3748/wjg.v28.i15.1508