Differential Expression of a Panel of Ten CNTN1-Associated Genes during Prostate Cancer Progression and the Predictive Properties of the Panel towards Prostate Cancer Relapse
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Culture
2.2. Western Blot Analysis
2.3. RNA Sequencing Analysis
2.4. Analysis of CNTN1-Associated Genes
2.5. Generation of CRPC in Animal Models
2.6. Patient Populations
2.7. Assignment of Signature Scores to Patients/Tumors and Cutoff Point Estimation
2.8. Statistical Analysis
3. Results
3.1. CNTN1-Mediated Promotion of LNCaP Cell Proliferation and Effects on Gene Expression
3.2. Differentional Expression of the 10 Leading-Edge Genes Following PC Progression
Gene | Gene Details | Log2 1 | p-Value | Function in PC | Refs |
---|---|---|---|---|---|
TMEM45B | transmembrane protein 45B | 12.2 | 0.0015 ** | a biomarker of PC progression and metastasis | [47] |
NANS | N-acetylneuraminic acid synthase | 11.9 | 0.0428 * | an androgen-responsive gene | [48] |
C1orf106 | chromosome 1 open reading frame 106 | 10.2 | 0.0428 * | unknown | NA |
LY75 | lymphocyte antigen 75 | 9.8 | 0.0164 * | not clear | NA |
ARFGEF2 | ADP-ribosylation factor guanine nucleotide-exchange factor 2 | 9.5 | 0.0101 * | protein detected in PC bone metastasis | [52] |
RNF144A | ring finger protein 144A | 3.2 | 0.0028 ** | not clear | NA |
GPR110 | G protein-coupled receptor 110 | 3.0 | 0.0152 * | an oncogene in PC | [49] |
FBXO6 | F-box protein 6 | 2.9 | 1.06 × 10−5 *** | unknown | NA |
PTPN3 | protein tyrosine phosphatase, non-receptor type 3 | 2.6 | 0.0065 ** | unknown | NA |
SRD5A3 | steroid 5 α-reductase 3 | 2.3 | 0.0027 ** | sustaining androgen biosynthesis in CRPC | [50,51] |
3.3. Differentional Expression of CNTN1 and LE Genes in CRPC
3.4. The LE Genes Predicting PC Relapse
3.5. Effective Prediction of PC Recurrence Using LE Genes as a Multigene Panel
3.6. The LE Panel as an Independent Risk Factor of PC Recurrence
3.7. LE Gene Panel Predicts Poor Overall Survival (OS) in Renal Cell Carcinoma (RCC) and Bladder Carcinoma
3.8. LE Gene Panel Predicts Poor OS in CNTN1-Associated Cancer Types
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Factors | Univariate Cox Analysis | Multivariate Cox Analysis | ||||
---|---|---|---|---|---|---|
HR | 95% CI | p-Value | HR | 95% CI | p-Value | |
LE Panel 1 | 2.72 | 1.96–3.37 | 1.77 × 10−9 *** | 1.91 | 1.37–2.671 | 0.000132 *** |
Age 2 | 1.02 | 0.99–1.05 | 0.189 | 0.99 | 0.96–1.02 | 0.6201 |
WHO IV 3 | 9.76 | 1.28–74.6 | 0.0282 * | 6.32 | 0.81–49.55 | 0.079158 |
WHO V 3 | 21.38 | 2.96–154.5 | 0.00241 ** | 10.28 | 1.36–77.77 | 0.024047 * |
Tstage 1 4 | 3.69 | 2.08–6.52 | 7.45 × 10−6 *** | 1.61 | 0.84–3.09 | 0.151878 |
Margin 1 5 | 2.30 | 1.52–3.48 | 8.1 × 10−5 *** | 1.32 | 0.84–2.08 | 0.228092 |
Factors | Univariate Cox Analysis | Multivariate Cox Analysis | ||||
---|---|---|---|---|---|---|
HR | 95% CI | p-Value | HR | 95% CI | p-Value | |
LE Panel 1 | 2.72 | 2.03–3.63 | 1.13 × 10−11 *** | 1.67 | 1.18–2.35 | 0.00341 ** |
Age 2 | 1.03 | 1.02–1.04 | 2.78 × 10−6 *** | 1.03 | 1.02–1.05 | 3.68 × 10−5 *** |
Sex 3 | 0.96 | 0.70–1.31 | 0.793 | 0.96 | 0.696–1.329 | 0.81224 |
Stage III 4 | 2.80 | 1.84–4.23 | 1.28 × 10−6 *** | 2.05 | 1.32–3.16 | 0.00127 ** |
Stage IV 4 | 6.83 | 4.60–10.12 | <2 × 10−16 *** | 4.53 | 2.87–7.13 | 7.13 × 10−11 *** |
Grade 3 5 | 1.94 | 1.32–2.86 | 0.000753 *** | 1.43 | 0.96–2.13 | 0.08017 |
Grade 4 5 | 5.74 | 3.59–8.05 | 3.06 × 10−16 *** | 2.01 | 1.25–3.23 | 0.00383 ** |
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Gu, Y.; Chow, M.J.; Kapoor, A.; Lin, X.; Mei, W.; Tang, D. Differential Expression of a Panel of Ten CNTN1-Associated Genes during Prostate Cancer Progression and the Predictive Properties of the Panel towards Prostate Cancer Relapse. Genes 2021, 12, 257. https://doi.org/10.3390/genes12020257
Gu Y, Chow MJ, Kapoor A, Lin X, Mei W, Tang D. Differential Expression of a Panel of Ten CNTN1-Associated Genes during Prostate Cancer Progression and the Predictive Properties of the Panel towards Prostate Cancer Relapse. Genes. 2021; 12(2):257. https://doi.org/10.3390/genes12020257
Chicago/Turabian StyleGu, Yan, Mathilda Jing Chow, Anil Kapoor, Xiaozeng Lin, Wenjuan Mei, and Damu Tang. 2021. "Differential Expression of a Panel of Ten CNTN1-Associated Genes during Prostate Cancer Progression and the Predictive Properties of the Panel towards Prostate Cancer Relapse" Genes 12, no. 2: 257. https://doi.org/10.3390/genes12020257
APA StyleGu, Y., Chow, M. J., Kapoor, A., Lin, X., Mei, W., & Tang, D. (2021). Differential Expression of a Panel of Ten CNTN1-Associated Genes during Prostate Cancer Progression and the Predictive Properties of the Panel towards Prostate Cancer Relapse. Genes, 12(2), 257. https://doi.org/10.3390/genes12020257