A Radiogenomic Approach for Decoding Molecular Mechanisms Underlying Tumor Progression in Prostate Cancer
Abstract
:1. Introduction
2. Results and Discussion
2.1. Description of the Radiogenomic Approach
2.2. Functional Characteristics of T2c and T3b Stages
2.3. Construction of the Prostate Cancer (PCa-GRN) Network
2.4. Functional Homogeneity within the Prostate Cancer (PCa-GRN) Network
2.5. Biomarker Identification
2.6. Correlation Analysis with Aggressiveness-Related Imaging Features
2.7. Assessing the Predictive Power of the Identified Biomarkers
3. Materials and Methods
3.1. Datasets
3.2. Data Pre-Processing
3.2.1. Genomic Data
3.2.2. Clinical Data
3.2.3. Imaging Data
3.3. Differential Expression and Association Analysis
3.4. Construction of Prostate-Specific GRN Network (PRAD-GRN)
3.5. Assessment of the Constructed Prostate Cancer (PCa-GRN) Network
3.5.1. Functional Homogeneity within the PCa-GRN Genes (Semantic Validation)
3.5.2. Enrichment Analysis of Genes and miRNAs
3.6. Correlation Analysis
3.7. Prediction Models
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Pathological STAGE | Count | Age Median (Min–Max) | PSA-Value Median (Min–Max) | Gleason Score | Count | Clinical Stage | Count | Biochemical Recurrence | Count | Ethnicity | Count |
---|---|---|---|---|---|---|---|---|---|---|---|
Primary + Secondary | Stage | ||||||||||
T2c | 164 | 59 (41–77) | 0.1 (0.01–14.69) | 3 + 3 | 25 | T1b | 0 | Yes | 6 | Black or African American | 3 |
3 + 4 | 84 | T1c | 84 | No | 131 | White | 58 | ||||
4 + 3 | 31 | T2 | 4 | Not available | 27 | Not available | 103 | ||||
≥8 | 24 | T2a | 16 | ||||||||
T2b | 10 | ||||||||||
T2c | 23 | ||||||||||
T3a | 2 | ||||||||||
T3b | 0 | ||||||||||
T4 | 0 | ||||||||||
Not available | 25 | ||||||||||
T3b | 134 | 62 (46–78) | 0.1 (0.01–37.36) | 3 + 3 | 1 | T1b | 2 | Yes | 29 | White | 27 |
3 + 4 | 8 | T1c | 23 | No | 94 | Not available | 107 | ||||
4 + 3 | 21 | T2 | 6 | Not available | 11 | ||||||
≥8 | 104 | T2a | 14 | ||||||||
T2b | 12 | ||||||||||
T2c | 16 | ||||||||||
T3a | 14 | ||||||||||
T3b | 16 | ||||||||||
T4 | 1 | ||||||||||
Not available | 30 |
Enriched Pathways Which Characterize the T2c Stage but Not the T3b Stage | ||
Pathways | Involved Genes | Adj-Pval |
hsa05218: Melanoma | FGF6, FGF8, FGF23, FGF3 | 3.00 × 10−3 |
hsa04010: MAPK signaling pathway | FGF6, DUSP4, FGF8, FGF23, FGF3, PLA2G4D | 3.00 × 10−3 |
hsa04810: Regulation of actin cytoskeleton | FGF6, FGF8, FGF23, MYLPF, FGF3 | 9.00 × 10−3 |
hsa04151: PI3K-Akt signaling pathway | FGF6, FGF8, COL6A5, FGF23, FGF3, EIF4E1B | 1.00 × 10−2 |
hsa04014: Ras signaling pathway | FGF6, FGF8, FGF23, FGF3, PLA2G4D | 1.1 × 10−2 |
hsa04015: Rap1 signaling pathway | FGF6, FGF8, FGF23, FGF3 | 4.7 × 10−2 |
Enriched Pathways Which Characterize the T3b Stage But Not the T2c Stage | ||
Pathways | Involved Genes | Adj-Pval |
hsa04080: Neuroactive ligand-receptor interaction | GABRD, MCHR1, GABRA2, GABRA3, GABRB2, ADCYAP1R1, GRIA3, NTSR2, GHRHR, HRH3, PRLR, GALR1, HRH2, P2RX2, NPFFR1, CHRNA1, ADRA1D, GABRQ | 2.23 × 10−5 |
hsa05033: Nicotine addiction | GABRD, GABRA2, GABRB2, GABRA3, GRIA3, GABRQ | 9.70 × 10−4 |
hsa04972: Pancreatic secretion | KCNMA1, CD38, ATP2B4, PLA2G2A, PLA2G2C, CPA1, ATP1A2, PRKCB | 2.09 × 10−3 |
hsa05143: African trypanosomiasis | IL6, HBA2, HBB, SELE, PRKCB | 3.58 × 10−3 |
hsa04727: GABAergic synapse | GABRD, PLCL1, GABRA2, GABRB2, GABRA3, GABRQ, PRKCB | 5.94 × 10−3 |
hsa04510: Focal adhesion | CAV3, CAV1, RASGRF1, PAK3, RAC3, ACTN2, ITGB3, FLNC, COL4A6, PRKCB, FN1 | 6.53 × 10−3 |
hsa04723: Retrograde endocannabinoid signaling | GABRD, GABRA2, GABRB2, GABRA3, GRIA3, GABRQ, PRKCB | 1.34 × 10−2 |
hsa05144: Malaria | IL6, CXCL8, HBA2, HBB, SELE | 1.46 × 10−2 |
hsa05146: Amoebiasis | GNAL, IL6, CXCL8, ACTN2, COL4A6, PRKCB, FN1 | 1.67 × 10−2 |
hsa04020: Calcium signaling pathway | GNAL, CD38, ATP2B4, ERBB4, HRH2, PLN, P2RX2, ADRA1D, PRKCB | 2.27 × 10−2 |
hsa04970: Salivary secretion | KCNMA1, CD38, ATP2B4, ATP1A2, ADRA1D, PRKCB | 2.53 × 10−2 |
hsa04270: Vascular smooth muscle contraction | KCNMA1, ACTG2, PLA2G2A, PLA2G2C, ADRA1D, KCNMB1, PRKCB | 2.77 × 10−2 |
hsa05032: Morphine addiction | GABRD, GABRA2, GABRB2, GABRA3, GABRQ, PRKCB | 3.14 × 10−2 |
hsa05205: Proteoglycans in cancer | CAV3, MIR10B, WNT16, CAV1, ERBB4, ITGB3, FLNC, PRKCB, FN1 | 4.02 × 10−2 |
hsa05412: Arrhythmogenic right ventricular cardiomyopathy (ARVC) | SGCG, DMD, ACTN2, ITGB3, CTNNA3 | 4.85 × 10−2 |
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Fischer, S.; Tahoun, M.; Klaan, B.; Thierfelder, K.M.; Weber, M.-A.; Krause, B.J.; Hakenberg, O.; Fuellen, G.; Hamed, M. A Radiogenomic Approach for Decoding Molecular Mechanisms Underlying Tumor Progression in Prostate Cancer. Cancers 2019, 11, 1293. https://doi.org/10.3390/cancers11091293
Fischer S, Tahoun M, Klaan B, Thierfelder KM, Weber M-A, Krause BJ, Hakenberg O, Fuellen G, Hamed M. A Radiogenomic Approach for Decoding Molecular Mechanisms Underlying Tumor Progression in Prostate Cancer. Cancers. 2019; 11(9):1293. https://doi.org/10.3390/cancers11091293
Chicago/Turabian StyleFischer, Sarah, Mohamed Tahoun, Bastian Klaan, Kolja M. Thierfelder, Marc-André Weber, Bernd J. Krause, Oliver Hakenberg, Georg Fuellen, and Mohamed Hamed. 2019. "A Radiogenomic Approach for Decoding Molecular Mechanisms Underlying Tumor Progression in Prostate Cancer" Cancers 11, no. 9: 1293. https://doi.org/10.3390/cancers11091293