Circulating miRNA as Biomarkers for Colorectal Cancer Diagnosis and Liver Metastasis
Abstract
:1. Introduction
2. Results
2.1. Characteristics of Study Subjects
2.2. Circulating miRNA Expression in Surgery Naïve Stage IV CRC Patients Compared to Healthy Subjects
2.3. Circulating miRNA Expression in Surgery Naïve vs. Postoperative and Recurrent Stage IV CRC Patients
2.4. Diagnostic Accuracy of miRNA for CRC Detection
2.5. Diagnostic Accuracy of miRNA for Liver Metastasis Detection
3. Discussion
4. Materials and Methods
4.1. Specimen Collection
4.2. Total RNA Extraction
4.3. miRNA Expression Using Reverse Transcription Quantitative Real Time Polymerase Chain Reaction (RT-qPCR)
4.4. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variable | All CRC Patients | Surgery Naïve | Postoperative | Recurrent | Healthy Subjects |
---|---|---|---|---|---|
Sample | 62 (58.5) | 33 (53.2) | 15 (24.2) | 14 (22.6) | 44 (41.5) |
Age (years) | 58 ± 13.49 | 56.3 ± 2.2 | 56.26 ± 13.86 | 63.9 ± 14.25 | 41.72 ± 8.97 |
BMI (kg/m2) | 27.17 ± 6.34 | 27.6 ± 6.37 | 25.1 ± 7.66 | 28.37 ± 4.35 | 26.39 ± 0.39 |
Gender | |||||
Male | 38 (61.3) | 21 (63.6) | 6 (40) | 11 (78.6) | 18 (40.9) |
Female | 24 (38.7) | 12 (36.4) | 9 (60) | 3 (21.4) | 26 (59.1) |
Nationality | |||||
Lebanese | 50 (82) | 27 (81.8) | 12 (85.7) | 11 (78.6) | 44 (100) |
Iraqi | 8 (13.1) | 5 (15.2) | 1 (7.1) | 2 (14.3) | |
Other | 3 (4.9) | 1 (3) | 1 (7.1) | 1 (7.1) | |
Smoking habits | |||||
No | 47 (75.8) | 26 (78.8) | 11 (73.3) | 11 (78.6) | 27 (61.4) |
Yes | 15 (24.2) | 7 (21.2) | 4 (26.7) | 3 (21.4) | 17 (38.6) |
Alcohol intake | |||||
No | 48 (77.4) | 26 (78.8) | 11 (73.3) | 11 (78.6) | 34 (81) |
Yes | 14 (22.6) | 7 (21.2) | 4 (26.7) | 3 (21.4) | 8 (19) |
Family Hx of Cancer | |||||
No | 35 (57.4) | 19 (57.6) | 7 (46.7) | 9 (64.3) | |
Yes | 26 (42.6) | 14 (42.4) | 8 (53.3) | 4 (30.8) | |
Tumor Sidedness | |||||
Left | 36 (60) | 24 (72.7) | 6 (42.9) | 6 (42.9) | |
Right | 15 (25) | 3 (9.1) | 7 (50) | 5 (35.7) | |
Rectum | 9 (15) | 5 (15.2) | 1 (7.1) | 3 (21.4) | |
Liver Mets | |||||
No | 15 (24.2) | 5 (15.2) | 4 (26.7) | 6 (42.9) | |
Yes | 47 (75.8) | 28 (84.8) | 11 (73.3) | 8 (57.1) | |
KRAS mutation | |||||
No | 26 (48.1) | 16 (53.3) | 5 (33.3) | 6 (50) | |
Yes | 28 (51.9) | 14 (46.7) | 8 (53.3) | 6 (50) | |
NRAS mutation | |||||
No | 46 (93.9) | 28 (93.3) | 9 (100) | 10 (90.9) | |
Yes | 3 (6.1) | 2 (6.7) | 0 | 1 (9.1) | |
BRAF mutation | |||||
No | 49 (100) | 28 (100) | 9 (100) | 11 (100) | |
Yes | 0 | 0 | 0 |
miRNA | AUC | SE | p-Value | 95% CI | Youden’s Index | Cut-Off | Sensitivity (%) | Specificity (%) | PPV (%) | NPV (%) | DA (%) |
---|---|---|---|---|---|---|---|---|---|---|---|
miR-210 | 0.682 | 0.055 | 0.003 | 0.574–0.79 | 0.288 | 10.46 | 44.7 | 84.1 | 75 | 56 | 62 |
miR-21 | 0.651 | 0.057 | 0.013 | 0.539–0.76 | 0.247 | 2.81 | 38.3 | 86.4 | 75 | 53 | 59 |
miR-210+21 | 0.731 | 0.052 | 0.0001 | 0.63–0.832 | 0.35 | 0.464 | 87.2 | 47.7 | 65 | 79 | 69 |
miRNA | AUC | SE | p-Value | 95% CI | Youden’s Index | Cut-Off | Sensitivity (%) | Specificity (%) | PPV (%) | NPV (%) | DA (%) |
---|---|---|---|---|---|---|---|---|---|---|---|
miR-19a | 0.746 | 0.091 | 0.014 | 0.569–0.924 | 0.485 | 6.025 | 66.7 | 81.8 | 93 | 45 | 72 |
miR-210 | 0.819 | 0.069 | 0.001 | 0.684–0.955 | 0.497 | 11.115 | 86.1 | 63.6 | 89 | 58 | 81 |
miR-203 | 0.797 | 0.063 | 0.003 | 0.673–0.92 | 0.611 | 15.65 | 61.1 | 100 | 100 | 44 | 70 |
miR-210+203 | 0.833 | 0.063 | 0.0009 | 0.711–0.956 | 0.576 | 0.838 | 66.7 | 90.9 | 96 | 45 | 72 |
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Nassar, F.J.; Msheik, Z.S.; Itani, M.M.; Helou, R.E.; Hadla, R.; Kreidieh, F.; Bejjany, R.; Mukherji, D.; Shamseddine, A.; Nasr, R.R.; et al. Circulating miRNA as Biomarkers for Colorectal Cancer Diagnosis and Liver Metastasis. Diagnostics 2021, 11, 341. https://doi.org/10.3390/diagnostics11020341
Nassar FJ, Msheik ZS, Itani MM, Helou RE, Hadla R, Kreidieh F, Bejjany R, Mukherji D, Shamseddine A, Nasr RR, et al. Circulating miRNA as Biomarkers for Colorectal Cancer Diagnosis and Liver Metastasis. Diagnostics. 2021; 11(2):341. https://doi.org/10.3390/diagnostics11020341
Chicago/Turabian StyleNassar, Farah J., Zahraa S. Msheik, Maha M. Itani, Remie El Helou, Ruba Hadla, Firas Kreidieh, Rachelle Bejjany, Deborah Mukherji, Ali Shamseddine, Rihab R. Nasr, and et al. 2021. "Circulating miRNA as Biomarkers for Colorectal Cancer Diagnosis and Liver Metastasis" Diagnostics 11, no. 2: 341. https://doi.org/10.3390/diagnostics11020341
APA StyleNassar, F. J., Msheik, Z. S., Itani, M. M., Helou, R. E., Hadla, R., Kreidieh, F., Bejjany, R., Mukherji, D., Shamseddine, A., Nasr, R. R., & Temraz, S. N. (2021). Circulating miRNA as Biomarkers for Colorectal Cancer Diagnosis and Liver Metastasis. Diagnostics, 11(2), 341. https://doi.org/10.3390/diagnostics11020341