CircEHD2, CircNETO2 and CircEGLN3 as Diagnostic and Prognostic Biomarkers for Patients with Renal Cell Carcinoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients
2.2. RNA Isolation, RNase R Treatment, and cel-miR-39 Spike-in
2.3. cDNA Synthesis and Quantitative Real-Time PCR
2.4. Statistics and Data Analysis
3. Results
3.1. Discovery Cohort
3.2. Validation Cohort
3.3. Analysis of circRNA Interactions
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Clinical Parameter | Discovery Cohort | Validation Cohort | ||
---|---|---|---|---|
ccRCC (n = 20) | Normal (n = 10) | ccRCC (n = 101) | Normal (n = 81) | |
Sex | ||||
male | 15 (75.0%) | 6 (60.0%) | 65 (64.4%) | 59 (72.8%) |
female | 5 (25.0%) | 4 (40.0%) | 36 (35.6%) | 22 (27.2%) |
Age | ||||
mean | 65.4 | 58.7 | 63.7 | 64.1 |
min-max | 43–78 | 43–78 | 36–89 | 36–89 |
pT-stage | ||||
pT1 | 10 (50.0%) | 61 (60.4%) | ||
pT2 | 0 (0%) | 11 (10.9%) | ||
pT3 | 9 (45.0%) | 28 (27.7%) | ||
pT4 | 1 (5.0%) | 1 (1.0%) | ||
lymph node metastasis | ||||
cN0/pN0 | 17 (85.0%) | 101 (100%) | ||
pN1 | 3 (15.0%) | 0 (0%) | ||
distant metastasis | ||||
cM0 | 10 (50.0%) | 95 (94.1%) | ||
cM1 | 10 (50.0%) | 6 (5.9%) | ||
Grading | ||||
grade 1 | 1 (5.0%) | 11 (10.9%) | ||
grade 2 | 12 (60.0%) | 74 (73.3%) | ||
grade 3 | 3 (15.0%) | 14 (13.9%) | ||
grade 4 | 4 (20.0%) | 2 (2.0%) |
Parameter | Univariate Analysis | Multivariate Analysis | ||
---|---|---|---|---|
p-Value | HR (95% CI) | p-Value | HR (95% CI) | |
Expression of circRNA | ||||
Low (<cut-off) | 1.00 | 1.00 | ||
High circEDEM2 | 0.246 | 1.68 (0.70–4.02) | ||
High circEGLN3 | 0.492 | 0.70 (0.26–1.92) | ||
High circEHD2 | 0.005 | 3.64 (1.48–8.92) | 0.009 | 3.58 (1.37–9.38) |
High circNETO2 | 0.002 | 0.26 (0.11–0.61) | 0.001 | 0.17 (0.60–0.50) |
Clinicopathological parameters | ||||
Grading | ||||
G1/2 | 1.00 | 1.00 | ||
G3/4 | <0.001 | 5.40 (2.29–12.72) | <0.001 | 9.40 (3.38–26.09) |
pT-stage | ||||
pT1/2 | 1.00 | 1.00 | ||
pT3/4 | 0.002 | 3.76 (1.61–8.75) | 0.009 | 3.32 (1.34–8.20) |
cM-stage | ||||
cM0 | 1.00 | 1.00 | ||
cM1 | 0.002 | 5.79 (1.94–17.25) | <0.001 | 11.91 (3.03–46.82) |
Parameter | Univariate Analysis | Multivariate Analysis | ||
---|---|---|---|---|
p-Value | HR (95% CI) | p-Value | HR (95% CI) | |
Expression of circRNA | ||||
Low (<cut-off) | 1.00 | 1.00 | ||
High circEDEM2 | 0.232 | 1.68 (7.16–3.97) | ||
High circEGLN3 | 0.883 | 0.938 (0.40–2.20) | ||
High circEHD2 | 0.005 | 3.64 (1.48–8.92) | 0.042 | 2.67 (1.04–6.85) |
High circNETO2 | 0.001 | 0.24 (0.10–0.56) | 0.001 | 0.14 (0.05–0.43) |
Clinicopathological parameters | ||||
Grading | ||||
G1/2 | 1.00 | 1.00 | ||
G3/4 | <0.001 | 5.40 (2.29–12.72) | <0.001 | 11.66 (3.95–34.40) |
pT-stage | ||||
pT1/2 | 1.00 | 1.00 | ||
pT3/4 | 0.002 | 3.76 (1.61–8.75) | 0.024 | 2.87 (1.15–7.17) |
cM-stage | ||||
cM0 | 1.00 | 1.00 | ||
cM1 | 0.002 | 5.78 (1.94–17.25) | <0.001 | 13.82 (3.386–56.39) |
Parameter | Univariate Analysis | Multivariate Analysis | ||
---|---|---|---|---|
p-Value | HR (95% CI) | p-Value | HR (95% CI) | |
Expression of circRNA | ||||
Low (<cut-off) | 1.00 | 1.00 | ||
High circEDEM2 | 0.541 | 1.30 (0.56–3.03) | ||
High circEGLN3 | 0.677 | 0.81 (0.30–2.21) | ||
High circEHD2 | 0.019 | 3.07 (1.20–7.85) | 0.008 | 3.91 (1.43–10.67) |
High circNETO2 | 0.010 | 0.32 (0.13–0.76) | 0.001 | 0.15 (0.05–0.46) |
Clinicopathological parameters | ||||
Grading | ||||
G1/2 | 1.00 | 1.00 | ||
G3/4 | <0.001 | 5.40 (2.29–12.72) | <0.001 | 9.95 (3.56–27.85) |
pT-stage | ||||
pT1/2 | 1.00 | 1.00 | ||
pT3/4 | 0.002 | 3.76 (1.61–8.75) | 0.007 | 3.52 (1.42–8.70) |
cM-stage | ||||
cM0 | 1.00 | 1.00 | ||
cM1 | 0.002 | 5.79 (1.94–17.25) | <0.001 | 14.03 (3.51–56.13) |
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Frey, L.; Klümper, N.; Schmidt, D.; Kristiansen, G.; Toma, M.; Ritter, M.; Alajati, A.; Ellinger, J. CircEHD2, CircNETO2 and CircEGLN3 as Diagnostic and Prognostic Biomarkers for Patients with Renal Cell Carcinoma. Cancers 2021, 13, 2177. https://doi.org/10.3390/cancers13092177
Frey L, Klümper N, Schmidt D, Kristiansen G, Toma M, Ritter M, Alajati A, Ellinger J. CircEHD2, CircNETO2 and CircEGLN3 as Diagnostic and Prognostic Biomarkers for Patients with Renal Cell Carcinoma. Cancers. 2021; 13(9):2177. https://doi.org/10.3390/cancers13092177
Chicago/Turabian StyleFrey, Lisa, Niklas Klümper, Doris Schmidt, Glen Kristiansen, Marieta Toma, Manuel Ritter, Abdullah Alajati, and Jörg Ellinger. 2021. "CircEHD2, CircNETO2 and CircEGLN3 as Diagnostic and Prognostic Biomarkers for Patients with Renal Cell Carcinoma" Cancers 13, no. 9: 2177. https://doi.org/10.3390/cancers13092177