A High-Accuracy Model Based on Plasma miRNAs Diagnoses Intrahepatic Cholangiocarcinoma: A Single Center with 1001 Samples
Abstract
:1. Introduction
2. Patients and Methods
2.1. Study Design and Patients
2.2. Quantification of Plasma miR-21 and miR-122
2.3. Model Construction and Validation
2.4. Statistical Analysis
2.5. Target Gene Prediction and Enrichment Analysis
3. Results
3.1. Patient Characteristics
3.2. The Expression of Plasma miR-21 and miR-122
3.3. Model Construction in Training Cohort
3.4. Model Validation
3.5. Function Prediction of miR21 and miR-122
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Characteristics | iCCA Cohort | ||
---|---|---|---|
Total iCCA (n = 359) | Radical Surgery (n = 266) | Liver Biopsy (n = 93) | |
Age > 60 yrs | 215 (59.9%) | 158 (59.4%) | 57 (61.3%) |
Male | 218 (60.7) | 160 (60.2%) | 58 (62.4%) |
Diagnosed by specimen after | |||
Radical surgery | 266 (74.1%) | 266 (100.0%) | − |
Liver resection | 261 (72.7%) | 261 (98.1%) | − |
Liver transplantation | 5 (1.4%) | 5 (1.9%) | − |
Liver biopsy | 93 (25.9%) | − | 93 (100.0%) |
Serum tumor biomarker, median (range) | |||
CA19-9 (IU/mL) | 57.2 (2.0–10,000.0) | 40.4 (2.0–10,000.0) | 339.0 (2.0–10,000.0) |
AFP (ng/mL) | 2.9 (0.9–19,998) | 2.9 (0.9–19,998) | 3.0 (0.9–1115.0) |
Tumor characteristics | |||
Tumor size (cm) | 5.44 (±2.96) | 4.87 (±2.78) | 7.09 (±2.90) |
Multiple | 73 (20.3%) | 50 (18.8%) | 23 (24.7%) |
Capsular invasion | − | 179 (67.3%) | − |
Perineural invasion | − | 69 (25.9%) | − |
MVI | − | 75 (28.2%) | − |
AJCC Stage II–IV | 169 (47.1%) | 93 (35.0%) | 76 (81.7%) |
Lymphatic metastasis | − | 42 (15.8%) | − |
Characteristics | iCCA Patients Receiving Radical Surgery (n = 266) | |||||
---|---|---|---|---|---|---|
Plasma miR-21 | Plasma miR-122 | |||||
Low (n = 133) | High (n = 133) | p | Low (n = 133) | High (n = 133) | p | |
Tumor size, cm | 0.030 | 0.096 | ||||
≤5 cm | 94 | 77 | 79 | 92 | ||
>5 cm | 39 | 56 | 54 | 41 | ||
Tumor number | 0.754 | 1.000 | ||||
Single | 107 | 109 | 108 | 108 | ||
Multiple | 26 | 24 | 25 | 25 | ||
Capsular invasion | ||||||
No | 39 | 48 | 36 | 51 | ||
Yes | 94 | 85 | 97 | 82 | ||
Microvascular invasion | 0.496 | 0.683 | ||||
No | 98 | 93 | 97 | 94 | ||
Yes | 35 | 40 | 36 | 39 | ||
Perineural invasion | ||||||
No | 98 | 99 | 101 | 96 | ||
Yes | 35 | 34 | 32 | 37 | ||
Lymphatic metastasis | ||||||
No | 112 | 112 | 107 | 117 | ||
Yes | 21 | 21 | 26 | 16 | ||
CA19-9 level, IU/mL | ||||||
≤ 34 | 63 | 63 | 64 | 62 | ||
> 34 | 70 | 70 | 69 | 71 | ||
AJCC Stage | 0.898 | 0.247 | ||||
0−I | 87 | 86 | 82 | 91 | ||
II−III | 46 | 47 | 51 | 42 |
Markers | iCCA vs. Control | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Training Cohort | Validation Cohort | |||||||||||
AUC (95% CI) | NPV (%) | PPV (%) | Sensitivity (%) | Specificity (%) | p | AUC (95% CI) | NPV (%) | PPV (%) | Sensitivity (%) | Specificity (%) | p | |
CA19-9 | 0.790 (0.757–0.820) | 72.1 | 87.7 | 62.6 | 86.3 | <0.001 | 0.805 (0.759–0.846) | 68.8 | 86.7 | 62.8 | 86.8 | <0.001 |
miR-21 | 0.773 (0.740–0.805) | 77.3 | 71.0 | 65.7 | 79.7 | <0.001 | 0.785 (0.737–0.828) | 72.5 | 65.0 | 72.9 | 70.6 | <0.001 |
miR-122 | 0.709 (0.673–0.744) | 73.7 | 65.5 | 56.5 | 70.7 | <0.001 | 0.707 (0.655–0.755) | 71.6 | 69.9 | 53.5 | 80.9 | <0.001 |
2-miR model * | 0.790 (0.757–0.820) | 80.1 | 73.9 | 63.9 | 84.7 | <0.001 | 0.801 (0.754–0.842) | 75.8 | 69.8 | 81.4 | 69.6 | <0.001 |
3-marker model # | 0.853 (0.824–0.879) | 83.3 | 86.5 | 73.0 | 87.4 | <0.001 | 0.866 (0.825–0.901) | 81.0 | 87.5 | 65.1 | 95.1 | <0.001 |
Markers | iCCA Cohort with Negative CA19-9 (n = 149) vs. Control (n = 571) | |||||
---|---|---|---|---|---|---|
AUC (95% CI) | NPV (%) | PPV (%) | Sensitivity (%) | Specificity (%) | p | |
miR-21 | 0.771 (0.739–0.802) | 83.4 | 80.4 | 77.2 | 65.8 | <0.001 |
miR-122 | 0.712 (0.677–0.725) | 81.8 | 82.1 | 63.8 | 74.1 | <0.001 |
2-miR model * | 0.794 (0.762–0.823) | 85.5 | 84.4 | 70.5 | 77.6 | <0.001 |
3-marker model # | 0.795 (0.763–0.824) | 85.9 | 85.1 | 76.5 | 72.7 | <0.001 |
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Hu, J.; Wang, Y.-N.; Song, D.-J.; Tan, J.-P.; Cao, Y.; Fan, J.; Wang, Z.; Zhou, J. A High-Accuracy Model Based on Plasma miRNAs Diagnoses Intrahepatic Cholangiocarcinoma: A Single Center with 1001 Samples. Diagnostics 2021, 11, 610. https://doi.org/10.3390/diagnostics11040610
Hu J, Wang Y-N, Song D-J, Tan J-P, Cao Y, Fan J, Wang Z, Zhou J. A High-Accuracy Model Based on Plasma miRNAs Diagnoses Intrahepatic Cholangiocarcinoma: A Single Center with 1001 Samples. Diagnostics. 2021; 11(4):610. https://doi.org/10.3390/diagnostics11040610
Chicago/Turabian StyleHu, Jie, Yi-Ning Wang, Dan-Jun Song, Jin-Peng Tan, Ya Cao, Jia Fan, Zheng Wang, and Jian Zhou. 2021. "A High-Accuracy Model Based on Plasma miRNAs Diagnoses Intrahepatic Cholangiocarcinoma: A Single Center with 1001 Samples" Diagnostics 11, no. 4: 610. https://doi.org/10.3390/diagnostics11040610