Proteotranscriptomic Discrimination of Tumor and Normal Tissues in Renal Cell Carcinoma
Abstract
:1. Introduction
2. Results
2.1. Database Setup
2.2. Genes Over-Expressed in ccRCC
2.3. Proteomic Analysis
2.4. Survival Analysis Using Proteome-Level Data
2.5. Validation Using Data from CPTAC
2.6. ccRCC-Specific Model Creation
3. Discussion
4. Materials and Methods
4.1. Gene Chip Database Comprising Normal and Tumor Tissues
4.2. Determining Differentially Expressed Genes
4.3. Ethics Statement
4.4. Sample Collection
4.5. Targeted Liquid Chromatography Coupled Tandem Mass Spectrometry (LC-MS/MS) Analysis
4.6. Statistical and Functional Analysis, Data Visualization
4.7. Building a Model for ccRCC Detection
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Semmelweis Cohort | Gene Chip Cohort | ||||
---|---|---|---|---|---|
Min age | 37 | Min age | 35 | ||
Median age | 62 | Median age | 64 | ||
Max age | 89 | Max age | 85 | ||
Mean age | 61.5 ± 10.8 | Mean age | 63.96 ± 13.12 | ||
Stage | N | % | Stage | N | % |
Stage I | 30 | 37% | Stage I | 46 | 22.2% |
Stage II | 8 | 9.9% | Stage II | 27 | 13% |
Stage III | 38 | 46.9% | Stage III | 29 | 14% |
Stage IV | 2 | 2.5% | Stage IV | 18 | 8.7% |
NA | 3 | 3.7% | NA | 87 | 57.9% |
Gender | N | % | Gender | N | % |
Male | 50 | 61.7% | Male | 40 | 19.2% |
Female | 31 | 38.3% | Female | 22 | 10.6% |
NA | 145 | 70.2 | |||
Race | N | Smoker | N | % | |
Caucasian | 81 | yes | 23 | 11.1% | |
no | 40 | 19.3% | |||
NA | 144 | 79.6% | |||
Obese | N | % | |||
yes | 19 | 9.2% | |||
no | 44 | 21.3% | |||
NA | 144 | 69.5% |
Gene Chip Cohort | SE-MS Cohort | |||
---|---|---|---|---|
Fold-Change | Adjusted p | Fold-Change | Adjusted p | |
ANXA1 | 2.89 | 1.02 ∗ 10−31 | 2.26 | 1.46 ∗ 10−13 |
ARHGDIB | 3.07 | 6.39 ∗ 10−32 | 1.68 | 4.83 ∗ 10−7 |
C1S | 3.64 | 1.40 ∗ 10−24 | 1.22 | 0.1042807 |
CCND1 | 4.12 | 4.09 ∗ 10−31 | 7.89 | 1.04 ∗ 10−24 |
FN1 | 5.21 | 5.24 ∗ 10-32 | 1.99 | 2.31 ∗ 10−8 |
GPNMB | 3.48 | 2.07 ∗ 10−28 | 2.11 | 1.02 ∗ 10−7 |
HLA-DPB1 | 3.45 | 3.13 ∗ 10−31 | 1.37 | 0.012 |
HLA-DRA | 3.17 | 1.44 ∗ 10−31 | 1.31 | 0.056 |
HMOX1 | 2.95 | 4.14 ∗ 10−28 | 1.32 | 0.081 |
HPCAL1 | 2.86 | 4.26 ∗ 10−31 | 1.75 | 5.33 ∗ 10−6 |
IGFBP3 | 8.15 | 5.88 ∗ 10−32 | 3.04 | 7.53 ∗ 10−18 |
LGALS1 | 4.57 | 5.24 ∗ 10−32 | 1.76 | 6.03 ∗ 10−8 |
LIPA | 3.07 | 5.24 ∗ 10−32 | 1.62 | 7.13 ∗ 10−7 |
MYOF | 2.86 | 5.24 ∗ 10−32 | 1.87 | 5.39 ∗ 10−8 |
P4HA1 | 2.96 | 5.24 ∗ 10−32 | 3.15 | 2.30 ∗ 10−22 |
PFKP | 5.69 | 5.24 ∗ 10−32 | 12.78 | 1.01 ∗ 10−47 |
PLIN2 | 3.85 | 3.09 ∗ 10−31 | 26.09 | 3.90 ∗ 10−39 |
PLOD2 | 4.21 | 5.24 ∗ 10−32 | 15.84 | 6.51 ∗ 10−36 |
RARRES2 | 3.35 | 2.11 ∗ 10−30 | 0.53 | 2.11 ∗ 10−7 |
TIMP1 | 3.61 | 5.24 ∗ 10−32 | 1.21 | 0.213 |
VEGFA | 3.02 | 5.11 ∗ 10−31 | 3.49 | 1.40 ∗ 10−22 |
VIM | 2.88 | 7.36 ∗ 10−32 | 2.06 | 4.09 ∗ 10−8 |
SE Data MS | CPTAC Protein Data | |||
---|---|---|---|---|
Fold-Change | Adjusted p-Value | Fold-Change | Adjusted p-Value | |
ANXA1 | 2.26 | 1.46 ∗ 10−13 | 2.31 | 6.60 ∗ 10−41 |
ARHGDIB | 1.68 | 4.83 ∗ 10−7 | 1.87 | 7.10 ∗ 10−42 |
C1S | 1.22 | 0.10 | 1.03 | 0.49 |
FN1 | 1.99 | 2.31 ∗ 10−8 | 1.91 | 1.90 ∗ 10−25 |
GPNMB | 2.11 | 1.02 ∗ 10−7 | 2.23 | 2.60 ∗ 10−17 |
HLA-DPB1 | 1.37 | 0.01 | 1.96 | 3.10 ∗ 10−32 |
HLA-DRA | 1.31 | 0.06 | 2.22 | 7.80 ∗ 10−36 |
HMOX1 | 1.32 | 0.08 | 1.67 | 1.20 ∗ 10−29 |
HPCAL1 | 1.75 | 5.33 ∗ 10−6 | 2.50 | 5.00 ∗ 10−45 |
IGFBP3 | 3.04 | 7.53 ∗ 10−18 | 2.28 | 2.10 ∗ 10−31 |
LGALS1 | 1.76 | 6.03 ∗ 10−8 | 1.77 | 1.60 ∗ 10−33 |
LIPA | 1.62 | 7.13 ∗ 10−7 | 1.91 | 9.40 ∗ 10−31 |
MYOF | 1.87 | 5.39 ∗ 10−8 | 1.88 | 2.00 ∗ 10−39 |
P4HA1 | 3.15 | 2.30 ∗ 10−22 | 3.20 | 9.90 ∗ 10−57 |
PFKP | 12.78 | 1.01 ∗ 10−47 | 4.20 | 4.30 ∗ 10−56 |
PLIN2 | 26.09 | 3.90 ∗ 10−39 | 6.92 | 1.70 ∗ 10−33 |
PLOD2 | 15.84 | 6.51 ∗ 10−36 | 4.89 | 7.40 ∗ 10−33 |
RARRES2 | 0.53 | 2.11 ∗ 10−7 | 0.76 | 1.20 ∗ 10−13 |
TIMP1 | 1.21 | 0.21 | 1.10 | 0.17 |
VEGFA | 3.49 | 1.40 ∗ 10−22 | 3.12 | 3.00 ∗ 10−32 |
VIM | 2.06 | 4.09 ∗ 10−8 | 2.27 | 1.70 ∗ 10−63 |
CCND1 | 7.89 | 1.04 ∗ 10−24 | - | - |
RF | SVM | KNN | LOGIT | |
---|---|---|---|---|
Accuracy | 0.958 | 0.979 | 0.9375 | 0.958 |
Kappa | 0.916 | 0.958 | 0.8750 | 0.916 |
Sensitivity | 0.916 | 0.958 | 0.8750 | 0.916 |
Specificity | 1.0 | 1.0 | 1.0 | 1.0 |
RF | PFKP | PLOD2 | PLIN2 | ||||||
SVM | PFKP | PLIN2 | PLOD2 | IGFBP3 | VEGFA | P4HA1 | CCND1 | VIM | ANXA1 |
KNN | PFKP | PLIN2 | PLOD2 | IGFBP3 | VEGFA | P4HA1 | CCND1 | ||
LOGIT | PFKP | PLIN2 | PLOD2 |
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Bartha, Á.; Darula, Z.; Munkácsy, G.; Klement, É.; Nyirády, P.; Győrffy, B. Proteotranscriptomic Discrimination of Tumor and Normal Tissues in Renal Cell Carcinoma. Int. J. Mol. Sci. 2023, 24, 4488. https://doi.org/10.3390/ijms24054488
Bartha Á, Darula Z, Munkácsy G, Klement É, Nyirády P, Győrffy B. Proteotranscriptomic Discrimination of Tumor and Normal Tissues in Renal Cell Carcinoma. International Journal of Molecular Sciences. 2023; 24(5):4488. https://doi.org/10.3390/ijms24054488
Chicago/Turabian StyleBartha, Áron, Zsuzsanna Darula, Gyöngyi Munkácsy, Éva Klement, Péter Nyirády, and Balázs Győrffy. 2023. "Proteotranscriptomic Discrimination of Tumor and Normal Tissues in Renal Cell Carcinoma" International Journal of Molecular Sciences 24, no. 5: 4488. https://doi.org/10.3390/ijms24054488