Two Single Nucleotide Polymorphisms in the Von Hippel-Lindau Tumor Suppressor Gene in Patients with Clear Cell Renal Cell Carcinoma
Abstract
:1. Introduction
2. Results
2.1. General Characteristics of Patients
2.2. Immunohistochemical Staining
2.3. Genotype and Allele Frequencies of VHL Polymorphisms in the ccRCC and Control European Population
2.4. Effects of VHL Polymorphisms on Clinicopathological Characteristics of ccRCC Patients
2.5. Associations of the VHL Polymorphisms with CD44, MMP-2 and MMP-9 Expression in ccRCC Tumors
2.6. Effects of VHL Polymorphisms on ccRCC Overall Survival
3. Discussion
4. Materials and Methods
4.1. Patient Characteristics and Tumor Samples
4.2. Immunohistochemical Staining and Its Evaluation
4.3. SNP Selection
4.4. DNA Extraction and Genotyping
4.5. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Clinicopathological Features | |
---|---|
Number of cases [n (%)] | 129 (100%) |
Age, years [mean ± SD] | 63 ± 10.7 |
Gender [n (%)] | |
Female | 53 (41.1%) |
Male | 76 (58.9%) |
Type of operation [n (%)] | |
Radical nephrectomy | 78 (60.5%) |
Partial nephrectomy (NSS) | 51 (39.5%) |
Tumor location [n (%)] | |
Right kidney | 71 (55.1%) |
Left kidney | 58 (44.9%) |
Tumor size, cm (mean ± SD) | 5.7 ± 3.4 |
Tumor stage [n (%)] | |
pT1 | 75 (58.1%) |
pT2 | 9 (6.9%) |
pT3 | 44 (34.1%) |
pT4 | 1 (0.9%) |
WHO/ISUP grading [n (%)] | |
G1 | 58 (44.9%) |
G2 | 47 (36.4%) |
G3 | 13 (10.2%) |
G4 | 11 (8.5%) |
Tumor necrosis area % (mean ± SD) | 5.7 ± 1.8 |
Sarcomatoid area % (mean ± SD) | 10.2 ± 2.86 |
Angioinvasion present [n (%)] | 27 (20.9%) |
Renal fibrous capsule invasion present [n (%)] | 73 (56.6%) |
Perinephric fat invasion present [n (%)] | 21 (16.3%) |
Renal sinus fat invasion present [n (%)] | 23 (17.8%) |
Renal sinus vascular invasion present [n (%)] | 18 (14.0%) |
Dead [n (%)] | 48 (37.2%) |
Overall Immunohistochemical Score | CD44 | MMP-2 | MMP-9 |
---|---|---|---|
Group 1 (low expression) [n (%)] | 93 (72.1%) | 127 (98.4%) | 127 (98.4%) |
Group 2 (moderate expression) [n (%)] | 24 (18.6%) | 2 (1.6%) | 1 (0.8%) |
Group 3 (high expression) [n (%)] | 12 (9.3%) | 0 (0%) | 1 (0.8%) |
Genotypes of rs1642742 | Cases Population | Database Control Population | p |
AA | 46.6% (n = 60) | 43.4% (n = 43) | NS |
AG | 17.8% (n = 23) | 48.5% (n = 48) | NS |
GG | 35.6% (n = 46) | 8.1% (n = 8) | NS |
Alleles of rs1642742 | Cases population | Database control population | |
A | 55% (n = 143) | 68% (n = 134) | NS |
G | 45% (n = 115) | 32% (n = 64) | NS |
Genotypes of rs779805 | Cases population | Database control population | |
AA | 47.2% (n = 61) | 43.4% (n = 43) | NS |
AG | 45.7% (n = 59) | 48.5% (n = 48) | NS |
GG | 7.1% (n = 9) | 8.1% (n = 8) | NS |
Alleles of rs779805 | Cases population | Database control population | |
A | 71% (n = 181) | 68% (n = 134) | NS |
G | 29% (n = 77) | 32% (n = 64) | NS |
Genotypes of rs1642742 | Tumor Size | Alleles of rs1642742 | Tumor Size | ||||||||
≤4 cm | 4–7 cm | 7–10 cm | >10 cm | p | ≤4 cm | 4–7 cm | 7–10 cm | >10 cm | p | ||
AA | 24.04% | 13.18% | 6.20% | 3.10% | NS | A | 28.91% | 14.50% | 8.53% | 3.49% | NS |
AG | 7.75% | 4.65% | 4.65% | 0.77% | NS | G | 12.40% | 16.28% | 7.75% | 8.14% | NS |
GG | 8.53% | 13.95% | 5.43% | 7.75% | NS | ||||||
p | NS | NS | NS | p = 0.05 | NS | NS | NS | NS | |||
Genotypes of rs779805 | Tumor size | Alleles of rs779805 | Tumor size | ||||||||
≤4 cm | 4–7 cm | 7–10 cm | >10 cm | ≤4 cm | 4–7 cm | 7–10 cm | >10 cm | ||||
AA | 24.04% | 13.95% | 6.20% | 3.10% | NS | A | 31.04% | 21.31% | 10.85% | 6.97% | NS |
AG | 13.95% | 14.73% | 9.30% | 7.75% | NS | G | 9.30% | 10.46% | 5.42% | 4.65% | NS |
GG | 2.34% | 3.10% | 0.77% | 0.77% | NS | ||||||
p | NS | NS | p = 0.048 | p = 0.05 | NS | NS | NS | NS |
Genotypes of rs1642742 | Tumor Stage | Alleles of rs1642742 | Tumor Stage | ||||||||
1 | 2 | 3 | 4 | p | 1 | 2 | 3 | 4 | p | ||
AA | 28.68% | 3.10% | 14.73% | 0% | p = 0.047 | A | 34.88% | 3.48% | 17.05% | 0% | NS |
AG | 12.42% | 0.77% | 4.65% | 0% | NS | G | 23.25% | 3.48% | 17.05% | 0.81% | NS |
GG | 17.05% | 3.10% | 14.73% | 0.77% | NS | ||||||
p | NS | NS | NS | NS | NS | NS | NS | NS | NS | ||
Genotypes of rs779805 | 1 | 2 | 3 | 4 | Alleles of rs779805 | 1 | 2 | 3 | 4 | ||
AA | 29.46% | 3.10% | 14.73% | 0% | NS | A | 41.86% | 4.49% | 23.83% | 0.38% | NS |
AG | 24.82% | 2.32% | 17.05% | 0.77% | NS | G | 16.28% | 1.93% | 10.85% | 0.38% | NS |
GG | 3.88% | 1.55% | 2.32% | 0% | NS | ||||||
p | NS | NS | NS | NS | p = 0.05 | NS | NS | NS |
Overall Immunohistochemical Score—CD44 | Overall Immunohistochemical Score—CD44 | ||||||
Genotypes of rs1642742 | Group 1 | Group 2 | Group 3 | Alleles of rs1642742 | Group 1 | Group 2 | Group 3 |
AA | 34.88% | 6.20% | 5.42% | A | 43.02% | 6.97% | 5.42% |
AG | 16.28% | 1.55% | 0% | G | 29.84% | 10.85% | 3.87% |
GG | 21.70% | 10% | 3.87% | ||||
p | NS | NS | NS | NS | NS | NS | |
Genotypes of rs779805 | Group 1 | Group 2 | Group 3 | Alleles of rs779805 | Group 1 | Group 2 | Group 3 |
AA | 35.65% | 6.20% | 5.42% | A | 51.94% | 11.24% | 6.97% |
AG | 32.55% | 10% | 3.10% | G | 20.93% | 6.58% | 2.32% |
GG | 4.65% | 1.55% | 0.77% | ||||
p | NS | NS | NS | NS | NS | NS | |
Overall immunohistochemical score—MMP-2 | Overall immunohistochemical score—MMP-2 | ||||||
Genotypes of rs164242 | Group 1 | Group 2 | Group 3 | Alleles of rs1642742 | Group 1 | Group 2 | Group 3 |
AA | 46.51% | 0% | 0% | A | 56.58% | 0% | 0% |
AG | 17.83% | 0% | 0% | G | 43.02% | 1.55% | 0% |
GG | 34.10% | 1.55% | 0% | ||||
p | NS | NS | NS | NS | NS | NS | |
Genotypes of rs779805 | Group 1 | Group 2 | Group 3 | Alleles of rs779805 | Group 1 | Group 2 | Group 3 |
AA | 47.28% | 0% | 0% | A | 69.40% | 0.77% | 0% |
AG | 44.18% | 1.55% | 0% | G | 29.06% | 0.77% | 0% |
GG | 6.97% | 0% | 0% | ||||
p | NS | NS | NS | NS | NS | NS | |
Overall immunohistochemical score—MMP-9 | Overall immunohistochemical score—MMP-9 | ||||||
Genotypes of rs1642742 | Group 1 | Group 2 | Group 3 | Alleles of rs1642742 | Group 1 | Group 2 | Group 3 |
AA | 46.51% | 0% | 0% | A | 55.81% | 0.38% | 0.38% |
AG | 17.05% | 0.77% | 0.77% | G | 43.41% | 0.38% | 0.38% |
GG | 34.88% | 0% | 0% | ||||
p | NS | NS | NS | NS | NS | NS | |
Genotypes of rs779805 | Group 1 | Group 2 | Group 3 | Alleles of rs779805 | Group 1 | Group 2 | Group 3 |
AA | 47.28% | 0% | 0% | A | 69.40% | 0.38% | 0.38% |
AG | 44.18% | 0.77% | 0.77% | G | 29.06% | 0.38% | 0.38% |
GG | 6.97% | 0% | 0% | ||||
p | NS | NS | NS | NS | NS | NS |
Deaths [n (%)] | Deaths [n (%)] | ||||||
Genotypes of rs1642742 | Yes [n (%)] | No [n (%)] | p | Alleles of rs1642742 | Yes [n (%)] | No [n (%)] | p |
AA | 19 (14.73%) | 41 (31.78%) | NS | A | 22 (17.05%) | 49 (37.98%) | NS |
AG | 6 (4.65%) | 17 (13.18%) | NS | G | 26 (20.16%) | 32 (24.81%) | NS |
GG | 23 (17.83%) | 23 (17.83%) | NS | ||||
Genotypes of rs779805 | p | Alleles of rs779805 | p | ||||
AA | 19 (14.73%) | 42 (32.55%) | NS | A | 30 (23.25%) | 61 (47.30%) | NS |
AG | 22 (17.05%) | 37 (28.67%) | NS | G | 18 (13.95%) | 20 (15.50%) | NS |
GG | 7 (5.44%) | 2 (1.56%) | NS |
Antibody | Clone | Source | Dilution |
---|---|---|---|
CD44 | Monoclonal | MRQ-13, Cell Marque, Rocklin, CA, USA | 1:300 |
MMP-2 | Monoclonal | CA-4001, Zeta Corporation, Arcadia, CA, USA | 1:50 |
MMP-9 | Monoclonal | EP127, Bio SB, Goleta, CA, USA | 1:100 |
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Chrabańska, M.; Szweda-Gandor, N.; Drozdzowska, B. Two Single Nucleotide Polymorphisms in the Von Hippel-Lindau Tumor Suppressor Gene in Patients with Clear Cell Renal Cell Carcinoma. Int. J. Mol. Sci. 2023, 24, 3778. https://doi.org/10.3390/ijms24043778
Chrabańska M, Szweda-Gandor N, Drozdzowska B. Two Single Nucleotide Polymorphisms in the Von Hippel-Lindau Tumor Suppressor Gene in Patients with Clear Cell Renal Cell Carcinoma. International Journal of Molecular Sciences. 2023; 24(4):3778. https://doi.org/10.3390/ijms24043778
Chicago/Turabian StyleChrabańska, Magdalena, Nikola Szweda-Gandor, and Bogna Drozdzowska. 2023. "Two Single Nucleotide Polymorphisms in the Von Hippel-Lindau Tumor Suppressor Gene in Patients with Clear Cell Renal Cell Carcinoma" International Journal of Molecular Sciences 24, no. 4: 3778. https://doi.org/10.3390/ijms24043778