Risk Classification of Bladder Cancer by Gene Expression and Molecular Subtype
Abstract
Simple Summary
Abstract
1. Introduction
2. Material and Methods
2.1. Study Population
2.2. Sample Collection and RNA Extraction
2.3. Gene Expression Custom Panel and NanoString Analysis
2.4. PD-L1 mRNA Quantification by RT-qPCR
2.5. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Variables | N (%) |
---|---|
Control | 5 (5.2) |
Tumor | 91 (94.8) |
Gender | |
Male | 85 (88.5) |
Female | 11 (11.5) |
Age, yr, median ± SD (range) | 73 ± 10.48 (43–95) |
Followup (median ± SD, range), in months | 46 ± 40.51 (2–125) |
Molecular Subtypes | |
Luminal | 65 (71.4) |
Basal | 19 (20.9) |
Null | 7 (7.7) |
Histologic Subtype | |
UC-conventional | 67 (73.6) |
UC-with variant histology | 24 (26.4) |
Clinical Subtypes | |
NMIBC | 66 (72.5) |
MIBC | 25 (27.5) |
Tumor stage * | |
Ta | 36 (39.5) |
T1 | 30 (33.0) |
T2-T4 | 25 (27.5) |
Tumor Grade (WHO 2022) | |
High-grade | 63 (69.2) |
Low-grade | 28 (30.8) |
PD-L1 expression | |
High expression | 36 (40) |
Low expression | 54 (60) |
Risk categories ** | |
Low | 14 (15.4) |
Intermediate | 13 (14.3) |
High | 38 (41.8) |
Very High | 26 (28.6) |
Recurrence event in NMIBC | |
Yes | 36 (54.5) |
No | 30 (45.5) |
Progression event in NMIBC | |
Yes | 7 (10.6) |
No | 59 (89.4) |
Survival (NMIBC and MIBC) | |
NED | 34 (37.4) |
AWD | 3 (3.3) |
DBC | 26 (28.6) |
DOC | 28 (30.7) |
Gene Descriptor | References | ||
---|---|---|---|
Prognosis | Target Therapy | ||
AKT1 | AKT serine/threonine kinase 1 | [27,28] | [29,30,31,32] |
ANXA10 | Annexin A10 | [33,34] | |
ARID1A | AT-Rich Interaction Domain 1A | [35,36,37,38,39] | |
BIRC3 | Baculoviral IAP Repeat Containing 3 | [40,41] | |
CCND1 | Cyclin D1 | [36,42] | |
CCND3 | Cyclin D3 | [36,43] | |
CDKN1A | Cyclin-dependent kinase inhibitor 1A (p21) | [27,44] | [44,45] |
CDKN1B | Cyclin-dependent kinase inhibitor 1B (p27, Kip1) | [46,47] | |
CDKN2A | Cyclin Dependent Kinase Inhibitor 2 (p16) | [27,38,48] | [48] |
DAB2 | Disabled homolog 2 | [34,49] | [50] |
EGFR | Epidermal growth factor receptor | [39,51,52] | [53] |
FGF2 | Fibroblast growth factor 2 | [54,55] | |
FGFR3 | Fibroblast growth factor receptor 3 | [19,27,36,37,39,56] | [53,57] |
HRAS | HRas proto-oncogene, GTPase | [27,36,58] | [59] |
HYAL2 | Hyaluronidase 2 | [34,60] | |
IDO1 | Indoleamine 2,3-dioxygenase 1 | [61,62] | [62,63] |
KDM6A | Lysine demethylase 6A | [27,56] | |
MAP4K1 | Mitogen-activated protein kinase kinase kinase kinase 1 | [34,64] | |
MKI67 | Marker of proliferation Ki-67 | [65,66] | |
NFE2L2 | NFE2 like bZIP transcription factor 2 | [56,67] | |
PIK3CA | Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha | [27,37,39,68] | [29,30,69] |
RB1 | RB transcriptional corepressor 1 | [39,56] | |
SPOCD1 | SPOC domain containing 1 | [34] | |
STAG2 | Stromal Antigen 2 | [70,71] | |
TERT | Telomerase reverse transcriptase | [27,72] | [73] |
TP53 | Tumor protein p53 | [27,37,38,39,74] | [45,74] |
VEGFA | Vascular endothelial growth factor A | [54,75] | [53] |
Gene | t-Test | FDR | AUC | Optimal Cut-Off |
---|---|---|---|---|
HRAS | <0.0001 | <0.0001 | 0.80 | 2.48 |
CDKN1A | <0.0001 | <0.0001 | 0.80 | 3.4 |
MAP4K1 | <0.0001 | <0.0001 | 0.79 | 2.01 |
NFE2L2 | <0.0001 | <0.0001 | 0.79 | 3.43 |
TP53 | <0.0001 | <0.0001 | 0.84 | 3.06 |
FGF2 | <0.0001 | <0.0001 | 0.80 | 1.86 |
IDO1 | <0.0001 | 0.0001 | 0.76 | 2.08 |
DAB2 | <0.0001 | 0.0002 | 0.77 | 3.16 |
FGFR3 | 0.0001 | 0.0002 | 0.81 | 3.29 |
ANXA10 | 0.0003 | 0.0008 | 0.75 | 3.05 |
CCND1 | 0.0008 | 0.0020 | 0.76 | 3.77 |
AKT1 | 0.0011 | 0.0024 | 0.73 | 3.56 |
SPOCD1 | 0.0012 | 0.0025 | 0.74 | 2.87 |
ARID1A | 0.0021 | 0.0041 | 0.68 | 2.93 |
MKI67 | 0.0023 | 0.0042 | 0.70 | 2.6 |
CCND3 | 0.0039 | 0.0065 | 0.71 | 2.71 |
BIRC3 | 0.0044 | 0.0070 | 0.68 | 2.28 |
VEGFA | 0.0150 | 0.0225 | 0.66 | 3.72 |
STAG2 | 0.0173 | 0.0246 | 0.57 | 3.09 |
Factors | β | HR | Score |
---|---|---|---|
Molecular subtypes | 1.277 | 3.584 | |
Luminal | 0 | ||
Basal/Null | 1 | ||
TP53 expression | −2.408 | 0.090 | |
High | 0 | ||
Low | 2 | ||
CCND1 expression | −2.710 | 0.067 | |
High | 0 | ||
Low | 2 | ||
MKI67 expression | 2.808 | 16.579 | |
High | 2 | ||
Low | 0 | ||
Total score | 0–7 |
Model A | |||||
Low Risk (score 0–2) | Intermediate Risk (score 3–4) | High Risk (score 5–7) | |||
43 (97.7%) NMIBC | 22 (66.7%) NMIBC | 1 (7.1%) NMIBC | |||
1 (2.3%) MIBC | 11 (33.3%) MIBC | 13 (92.9%) MIBC | |||
Model B | |||||
Low Risk (score 0–2) | High Risk (score 3–7) | ||||
43 (97.7%) NMIBC | 23 (48.9%) NMIBC | ||||
1 (2.3%) MIBC | 24 (51.1%) MIBC |
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Blanca, A.; Lopez-Beltran, A.; Lopez-Porcheron, K.; Gomez-Gomez, E.; Cimadamore, A.; Bilé-Silva, A.; Gogna, R.; Montironi, R.; Cheng, L. Risk Classification of Bladder Cancer by Gene Expression and Molecular Subtype. Cancers 2023, 15, 2149. https://doi.org/10.3390/cancers15072149
Blanca A, Lopez-Beltran A, Lopez-Porcheron K, Gomez-Gomez E, Cimadamore A, Bilé-Silva A, Gogna R, Montironi R, Cheng L. Risk Classification of Bladder Cancer by Gene Expression and Molecular Subtype. Cancers. 2023; 15(7):2149. https://doi.org/10.3390/cancers15072149
Chicago/Turabian StyleBlanca, Ana, Antonio Lopez-Beltran, Kevin Lopez-Porcheron, Enrique Gomez-Gomez, Alessia Cimadamore, Andreia Bilé-Silva, Rajan Gogna, Rodolfo Montironi, and Liang Cheng. 2023. "Risk Classification of Bladder Cancer by Gene Expression and Molecular Subtype" Cancers 15, no. 7: 2149. https://doi.org/10.3390/cancers15072149
APA StyleBlanca, A., Lopez-Beltran, A., Lopez-Porcheron, K., Gomez-Gomez, E., Cimadamore, A., Bilé-Silva, A., Gogna, R., Montironi, R., & Cheng, L. (2023). Risk Classification of Bladder Cancer by Gene Expression and Molecular Subtype. Cancers, 15(7), 2149. https://doi.org/10.3390/cancers15072149