Loss of CDKN1A mRNA and Protein Expression Are Independent Predictors of Poor Outcome in Chromophobe Renal Cell Carcinoma Patients
Abstract
:1. Introduction
2. Results
2.1. Chromosomal Loss and Patient Outcome
2.2. Identification of Genes Associated with Chromosomal Loss, Decreased Expression and Patient Survival
2.3. CDKN1A mRNA and Protein Expression
2.4. CDKN1A Expression, Tumor Stage, Grade and Outcome
3. Discussion
4. Materials and Methods
4.1. Data Acquisition and Processing Using the Cancer Genome Atlas Data Portal
4.2. Strategy for Gene Candidate Selection
4.3. Swiss Chromophobe Renal Cell Carcinomas
4.4. OncoScan Assay
4.5. Immunohistochemistry
4.6. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Gene Name | Chromosomal Locus 1 | CNV vs mRNA Pearson’s Correlation Coefficient 2 | Protein Expression 3 | Protein Function (GeneCards 4) |
---|---|---|---|---|
CDKN1A | 6p21.2 | R = 0.4434, p = 0.0002 | nucleus | Cell cycle regulation |
KLF6 | 10p15.2 | R = 0.5474, p < 0.0001 | nucleus | Transcriptional activator |
FAM160B1 | 10q25.3 | R = 0.7632, p < 0.0001 | cytoplasm | unknown |
PAOX | 10q26.3 | R = 0.6088, p < 0.0001 | cytoplasm | Polyamine oxidase |
PWWP2B | 10q26.3 | R = 0.52, p < 0.0001 | cytoplasm | unknown |
FBXW4 | 10q24.32 | R = 0.4296, p = 0.0003 | golgi | Ubiquitination |
FBXL15 | 10q24.32 | R = 0.4048, p = 0.0007 | cytoplasm | Ubiquitination |
CASKIN2 | 17q25.1 | R = 0.4364, p = 0.0002 | cytoplasm | unknown |
RTN4RL1 | 17p13.3 | R = 0.4013, p = 0.0008 | secreted | Brain development |
FMNL1 | 17q21.31 | R = 0.3974. p = 0.001 | cytoplasm | Regulation of cell morphology |
RAB37 | 17q25.1 | R = 0.369, p = 0.002 | cytoplasm | GTPase |
SOCS3 | 17q25.3 | R = 0.3611, p = 0.003 | cytoplasm | Cytokine signaling suppression |
C21orf2 | 21q22.3 | R = 0.5435, p < 0.0001 | mitochondria | Regulation of cell morphology, DNA damage repair |
Cohort | TCGA-KICH | Swiss Patients | ||||||
---|---|---|---|---|---|---|---|---|
Variables | Univariate | Multivariate2 | Univariate | Multivariate | ||||
HR (95%CI) | p-value | HR (95%CI) | p-value | HR (95%CI) | p-value | HR (95%CI) | p-value | |
Tumor stage (3–4 vs 1–2) 1 | 10.22 (2.12–49.29) | 0.004 | 6.442 (1.488–37.214) | 0.012 | 1.447 (0.398–5.264) | n.s. | 1.266 (0.343–4.678) | n.s. |
Grade (High vs Low) | 18.03 (4.448–73.05) | <0.001 | 6.087 (1.374–32.266) | 0.017 | - | - | - | - |
CDKN1A expression (Low vs High) 2, 3 | 22.528 (2.862–2904.443) | <0.001 | 12.527 (1.289–1675.059) | 0.026 | 4.812 (1.07–21.64) | <0.05 | 4.741 (1.051–21.390) | <0.05 |
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Ohashi, R.; Angori, S.; Batavia, A.A.; Rupp, N.J.; Ajioka, Y.; Schraml, P.; Moch, H. Loss of CDKN1A mRNA and Protein Expression Are Independent Predictors of Poor Outcome in Chromophobe Renal Cell Carcinoma Patients. Cancers 2020, 12, 465. https://doi.org/10.3390/cancers12020465
Ohashi R, Angori S, Batavia AA, Rupp NJ, Ajioka Y, Schraml P, Moch H. Loss of CDKN1A mRNA and Protein Expression Are Independent Predictors of Poor Outcome in Chromophobe Renal Cell Carcinoma Patients. Cancers. 2020; 12(2):465. https://doi.org/10.3390/cancers12020465
Chicago/Turabian StyleOhashi, Riuko, Silvia Angori, Aashil A. Batavia, Niels J. Rupp, Yoichi Ajioka, Peter Schraml, and Holger Moch. 2020. "Loss of CDKN1A mRNA and Protein Expression Are Independent Predictors of Poor Outcome in Chromophobe Renal Cell Carcinoma Patients" Cancers 12, no. 2: 465. https://doi.org/10.3390/cancers12020465