Genomic Landscape of Vinflunine Response in Metastatic Urothelial Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Methods
2.1. Patients
2.2. Next Generation Sequencing and Variant Calling
2.3. Gene Expression Profiles
2.4. Immunohistochemistry and Real Time Quantitative PCR for MAGEA4
2.5. Statistical Analysis
2.6. Data Availability
3. Results
3.1. Clinical Characteristics
3.2. Somatic Genetic Alterations
3.3. Tumour Immune Expression Is Associated with Differences in Vinflunine Efficacy
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Responders | Non-Responders (n = 11) | Global | p Value | |
---|---|---|---|---|
(n = 12) | (n = 23) | |||
Male (%)/Female (%) | 11 (19%)/1 (9%) | 8 (72%)/3 (28%) | 19 (82%)/4 (18%) | 0.23 |
Age media (SD) | 67 (9.2) | 66 (11.4) | 66 | 0.57 |
Smokers | 8 (66%) | 7 (63%) | 15 (65%) | 0.54 |
Urothelial carcinoma | 12 (100%) | 11 (100) | 100 (100%) | |
1 Line | ||||
0 | 6 (50%) | 5 (45%) | 11 (48%) | |
1 | 6 (50%) | 5 (45%) | 11 (48%) | |
2 | 0 | 1 (10%) | 1 (4%) | 0.56 |
Prior platinum based CT | ||||
Cisplatin | 10 (83%) | 5 (45%) | 15 (65%) | |
Carboplatin | 2 (17%) | 6 (55%) | 8 (35%) | 0.06 |
Response to platinum based CT | ||||
Partial response | 1 (8%) | 5 (45%) | 6 (26%) | |
Stable disease | 6 (50%) | 5 (45%) | 11 (48%) | |
Progressive disease | 5 (42%) | 1 (9%) | 6 (26%) | 0.06 |
Number of line for vinflunine | ||||
2 | 9 (81%) | 10 (90%) | 19 (83%) | |
3 | 1 (8%) | 1 (9%) | 2 (8.6%) | |
4 | 2 (16%) | 0 | 2 (8.6%) | 0.36 |
Location of metastases | ||||
Lung | 5 (42%) | 4 (36%) | 9 (39%) | 0.79 |
Lymph nodes | 9 (81%) | 7 (27%) | 16 (69%) | 0.55 |
Liver | 1 (8%) | 3 (45%) | 4 (17%) | 0.23 |
Bone | 4 (36%) | 5 (27/) | 9 (39%) | 0.52 |
Median PFS (months) of vinflunine treatment (CI 95%) | 10 (8.7–11.5) | 2.2 (1.8–2.5) | 6 (0–15.5) | 0.02 |
Median OS (months) of vinflunine treatment | 19.9 (10.7–29.0) | 2.5 (2.1–2.8) | 11.5 (3.4–19.5) | 0.06 |
Gene | Log2 Fold Change | Std Error (log2) | Lower Confidence Limit (log2) | Upper Confidence Limit (log2) | p-Value | BY.p-Value | Gene.Sets |
---|---|---|---|---|---|---|---|
MAGEA12- | 3.58 | 0.726 | 2.16 | 5 | 0.0000927 | 0.485 | CT Antigen |
IFIT1- | 1.99 | 0.458 | 1.09 | 2.89 | 0.000311 | 0.497 | Chemokines |
ISG15- | 1.58 | 0.375 | 0.84 | 2.31 | 0.000442 | 0.497 | |
IFITM1 | 1.89 | 0.452 | 1 | 2.77 | 0.000464 | 0.497 | Regulation |
IFI27- | 2.27 | 0.555 | 1.19 | 3.36 | 0.000557 | 0.497 | Chemokines |
MAGEA4- | 2.69 | 0.652 | 1.41 | 3.97 | 0.00057 | 0.497 | CT Antigen |
Immune Pathway | Signature Scores (NR/R) |
---|---|
Regulation | 3.52 |
Chemokines | 3.22 |
Cytokines | 2.06 |
Cell Functions | 1.94 |
T-Cell Functions | 1.83 |
TNF Superfamily | 1.59 |
Antigen Processing | 1.43 |
Pathogen Defense | 1.40 |
Interleukins | 1.30 |
Adhesion | 1.29 |
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Bernardini, A.; Dueñas, M.; Martín-Soberon, M.C.; Rubio, C.; Suarez-Cabrera, C.; Ruiz-Palomares, R.; Munera-Maravilla, E.; Lázaro, S.; Lodewijk, I.; Rueda, D.; et al. Genomic Landscape of Vinflunine Response in Metastatic Urothelial Cancer. Cancers 2022, 14, 378. https://doi.org/10.3390/cancers14020378
Bernardini A, Dueñas M, Martín-Soberon MC, Rubio C, Suarez-Cabrera C, Ruiz-Palomares R, Munera-Maravilla E, Lázaro S, Lodewijk I, Rueda D, et al. Genomic Landscape of Vinflunine Response in Metastatic Urothelial Cancer. Cancers. 2022; 14(2):378. https://doi.org/10.3390/cancers14020378
Chicago/Turabian StyleBernardini, Alejandra, Marta Dueñas, María Cruz Martín-Soberon, Carolina Rubio, Cristian Suarez-Cabrera, Raquel Ruiz-Palomares, Ester Munera-Maravilla, Sara Lázaro, Iris Lodewijk, Daniel Rueda, and et al. 2022. "Genomic Landscape of Vinflunine Response in Metastatic Urothelial Cancer" Cancers 14, no. 2: 378. https://doi.org/10.3390/cancers14020378