Metabolomic Signatures of Treatment Response in Bladder Cancer
Abstract
:1. Introduction
2. Bladder Cancer
2.1. Epidemiology and Risk Factors
2.2. Histologic Variants, Stages and Molecular Subtypes
2.3. Diagnosis and Prognosis
2.4. Treatment and Management
2.4.1. TURBT and Radical Cystectomy
2.4.2. Immunotherapy
2.4.3. Chemotherapy
3. Tracking Treatment Response in BC Using Metabolomics Approaches
3.1. Metabolomics Workflow
Techniques | Advantages | Disadvantages |
---|---|---|
GC-MS | High resolution High sensitivity High accuracy High repeatability High discrimination between similar molecules | Ineffective on thermolabile compounds Needs derivatization of non-volatile metabolites Slightly expensive |
LC-MS | Good resolution High sensitivity Effective on thermolabile compounds | Lack of standard spectral libraries Adducts formation Long analytical time Slightly expensive |
NMR | Non-destructive analysis High reproducibility Relatively simple sample preparation Highly quantitative Relatively fast | Low sensitivity Peak overlapping Very expensive |
3.2. Metabolomic Biomarkers of Treatment Response in BC
3.2.1. In Vitro Studies
Cell Lines | Treatment | Study Groups | Analytical Techniques | Main Results | References |
---|---|---|---|---|---|
Transitional Cell Carcinoma (T24) | Cisplatin (chemotherapy) | T24S: Cisplatin-sensitive T24 T24R: Cisplatin-resistant T24 T24S−: Cisplatin-sensitive without ACSS2 inhibitor T24 S+: Cisplatin-sensitive with ACSS2 inhibitor T24R−: Cisplatin-resistant without ACSS2 inhibitor T24 R+: Cisplatin-resistant with ACSS2 inhibitor | UPLC-MS | T24R vs. T24S: ↑ CE (22:6); PC (35:4); PC (36:6); SM (d42:2); SM (d42:3); SM (d32:1) ↓ PE (p-36:4)/PE (o-36:5); PE (p-38:4)/PE (o-38:5); PE (p-40:5)/PE (o-40:6); TG (48:0); TG (49:0); TG (49:0); TG (49:1); TG (50:0); TG (52:0); TG (54:5) T24S+ vs. T24S− and T24R+ vs. T24R−: ↓ CE (22:6); CE (18:1); TG (49:1); TG (53:2) | Lee et al., 2018 [106] |
Transitional Cell Carcinoma (T24) | Cisplatin (chemotherapy) | T24S: Cisplatin-sensitive T24 T24R: Cisplatin-resistant T24 | 2D NMR (1H-13C Heteronuclear Single Quantum Coherence) | T24R cells exhibited: Higher glucose consumption Higher and faster acetate accumulation Higher levels of fatty acids Lower production and excretion of lactate T24S cells exhibited: Higher and faster lactate and alanine accumulation | Wen et al., 2019 [105] |
Transitional Cell Carcinoma (T24) | Pirarubicin (chemotherapy) | T24: Parental T24 T24/THP: Pirarubicin-resistant T24 | LC-MS | T24/THP vs. T24: Dysregulations in the levels of more than 200 metabolites (annotation not provided), including lower levels of putrescine and spermidine Arginine and proline metabolism pathway showed the strongest correlation with the differential metabolites | Zhu et al., 2022 [107] |
3.2.2. Human Biofluid and Tissue Studies
Biological Matrix | Treatment | Study Groups | Analytical Techniques | Main Results | References |
---|---|---|---|---|---|
Serum | TURBT (surgery) | Pre-operative: LG, n = 35; HG, n = 31 Post-operative: LG, n = 33; HG, n = 31 Controls, n = 52 | 1H NMR | Post- vs. pre-operative LG: ↓ DMA, lactate, glutamine, histidine, valine Post- vs. pre-operative HG: ↓ DMA, lactate, histidine, valine, malonate The levels of DMA, glutamine and malonate are similar to those of controls at 90 days after surgery | Gupta et al., 2020 [113] |
Urine | TURBT (surgery) | NMIBC patients: Pre-TURBT, n = 10 Post-TURBT, n = 10 | HPLC-MS GC-MS | Post- (2 weeks) vs. pre-TURBT: ↓ N-Acetylneuraminic acid, androsterone 3-glucuronide, creatine riboside, creatinine, 5,6-dihydrouridine, N6,N6-dimethyl-lysine, 1,3-dimethyluracil, glucosylgalactosyl hydroxylysine, glutarylcarnitine, guanidinosuccinic acid, indolelactic acid, indoxyl sulfate, N6-methyladenosine, 3-methylglutarylcarnitine, 1-methylguanine, 1-methylinosine, N6-methyl-lysine, succinylcarnitine, N-methylnicotinamide, N-methylnicotinamide, glutamic acid, O-sebacoylcarnitine, succinyladenosine, tryptophan, valine | Jacyna et al., 2022 [114] |
Bladder tissue | Gemcitabine (chemotherapy) | Pre-gemcitabine: BC, n = 12 (Ta n = 2, T1 n = 1, and T2 n = 9); normal, n = 12 Post-gemcitabine: BC, n = 12 (Ta n = 2, T1 n = 1, and T2 n = 9); normal, n = 12 | UPLC-MS | Among the 34 BC-associated metabolites (pre-gemcitabine BC vs. pre-gemcitabine normal), the levels of bilirubin and retinal recovered after gemcitabine treatment (post-gemcitabine BC vs. pre-gemcitabine normal) Histamine (↑) and thiamine (↓) levels found altered in adjacent normal tissue after gemcitabine treatment | Yang et al., 2019 [115] |
Serum | Gemcitabine and cisplatin (neoadjuvant chemotherapy) | MIBC patients: NAC-sensitive, n = 6 (T2 n = 4, and T3 n = 2) NAC-resistant, n = 12 (T2 n = 5, T3 n = 6, and T4 n= 1) | 1H NMR UPLC-MS | NAC-sensitive vs. NAC-resistant: ↑ Glutamine, taurine ↓ 2-Hydroxy-3-methylvalerate, 3-methyl-2-oxovalerate, 3-hydroxybutyrate, alanine, glutamate, pyruvate, pyroglutamate, glycine, hypoxanthine | Zhuang et al., 2022 [116] |
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Primary Tumor (T) | |
---|---|
TX | Primary tumor cannot be assessed |
T0 | No evidence of tumor |
Ta | Non-invasive papillary carcinoma |
Tis | Carcinoma in situ (CIS) |
T1 | Tumor invades subepithelial connective tissue |
T2 | Tumor invades muscle |
T2a | Tumor invades superficial muscle |
T2b | Tumor invades deep muscle |
T3 | Tumor invades perivesical tissue |
T3a | Microscopically |
T3b | Macroscopically |
T4 | Tumor invades other tissues |
T4a | Tumor invades prostate stroma, seminal vesicles, uterus, or vagina |
T4b | Tumor invades pelvic or abdominal wall |
Regional nymph nodes (N) | |
NX | Regional lymph nodes cannot be assessed |
N0 | Regional lymph nodes without metastasis |
N1 | Metastasis in a single lymph node in the true pelvis |
N2 | Metastasis in multiple regional lymph nodes in the true pelvis |
N3 | Metastasis in common iliac lymph nodes |
Distant metastasis (M) | |
M0 | No distant metastasis |
M1a | Non-regional lymph nodes |
M1b | Other distant metastasis |
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© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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Vieira de Sousa, T.; Guedes de Pinho, P.; Pinto, J. Metabolomic Signatures of Treatment Response in Bladder Cancer. Int. J. Mol. Sci. 2023, 24, 17543. https://doi.org/10.3390/ijms242417543
Vieira de Sousa T, Guedes de Pinho P, Pinto J. Metabolomic Signatures of Treatment Response in Bladder Cancer. International Journal of Molecular Sciences. 2023; 24(24):17543. https://doi.org/10.3390/ijms242417543
Chicago/Turabian StyleVieira de Sousa, Tiago, Paula Guedes de Pinho, and Joana Pinto. 2023. "Metabolomic Signatures of Treatment Response in Bladder Cancer" International Journal of Molecular Sciences 24, no. 24: 17543. https://doi.org/10.3390/ijms242417543