Urinary Metabolic Signatures Detect Recurrences in Non-Muscle Invasive Bladder Cancer

Loras, Alba; Martínez-Bisbal, M. Carmen; Quintás, Guillermo; Gil, Salvador; Martínez‐Máñez, Ramón; Ruiz-Cerdá, J.L.

doi:10.3390/cancers11070914

Cited by 20 publications

(15 citation statements)

References 41 publications

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“…Furthermore, A 32-metabolite/resonance signature descriptive of RCC was unveiled, successfully distinguishing RCC patients from controls in principal component analysis. This work demonstrates the value of a systematic metabolomics workflow for the identification of the robust urinary metabolic biomarkers of RCC (18).…”

Section: Discussionmentioning

confidence: 78%

The Clinical Experiences of Urine Metabolomics of Genitourinary Urothelial Cancer in a Tertiary Hospital in Taiwan

et al. 2021

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Few studies have addressed the impact of diagnostic urine metabolites and the clinical outcomes associated with genitourinary urothelial (GU) cancer to date. Furthermore, longitudinal analysis of the dynamics of urine metabolites contributing to the detection of GU cancer has not yet been fully investigated; therefore, the discovery of novel diagnostic urine biomarkers is of enormous interest. We explored the correlation of the urine metabolomic profiles to GU cancers. The aqueous metabolites of the GU cancer and the control were also identified and analyzed through high-resolution1H nuclear magnetic resonance (NMR) spectroscopy. Compared with the control, the urine metabolites of the tumor were studied in relation to changes over time in a linear mixed model for repeated measures. The urine metabolites of sixty-three (44 male and 19 female) patients with GU cancers were systemically analyzed. The urine metabolite profile in GU cancer was significantly higher than those in the control group (p<0.05). Sevenurine metabolites including histidine, propylene glycol, valine, leucine, acetylsalicylate, glycine, and isoleucine as well as other pathways were identified statistically and were significantly associated with GU cancer detection with longitudinal analysis. We discovered that histidine, propylene glycol, valine, leucine, acetylsalicylate, glycine, isoleucine, succinic acid, lysine2-aminobutyric acid, and acetic acid are involved significantly in all types of male patients in whom the type (upper tract) of urine metabolites were found to be statistically significant compared with the control. We did not find any statistical significance in urine biomarkers between female and male patients. However, a statistically insignificant correlation was found among the grade and stage with the metabolites.

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Section: Discussionmentioning

confidence: 78%

The Clinical Experiences of Urine Metabolomics of Genitourinary Urothelial Cancer in a Tertiary Hospital in Taiwan

et al. 2021

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“…It is important to note that all these discriminant metabolites were identified in studies where tumor and non-tumor samples were compared, so clinically they could be applied as diagnostic biomarkers. Conversely, other studies identified metabolites related to BC aggressiveness using samples from LG or HG tumors [ 44 , 234 , 235 , 236 ]. For instance, Bensal et al identified a serum metabolic profile composed of six metabolites (dimethyl amine (DMA), malonate, lactate, glutamine, histidine, and valine) able to distinguish LG and HG BC samples from control samples.…”

Section: Non-invasive Bladder Cancer Biomarkersmentioning

confidence: 99%

“…For instance, Bensal et al identified a serum metabolic profile composed of six metabolites (dimethyl amine (DMA), malonate, lactate, glutamine, histidine, and valine) able to distinguish LG and HG BC samples from control samples. All except malonate were identified as crucial to segregate LG tumors from controls; DMA, malonate, lactate, and histidine served as differentiating biomarkers of HG from controls and the combination of DMA, glutamine, and malonate was sufficient to accurately segregate LG from HG [ 236 ]. Tan et al also performed a metabolomic study using serum samples of patients with LG and HG BC.…”

Section: Non-invasive Bladder Cancer Biomarkersmentioning

confidence: 99%

Epigenomic and Metabolomic Integration Reveals Dynamic Metabolic Regulation in Bladder Cancer

Loras

Segovia

Ruiz-Cerdá

2021

Cancers

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Bladder cancer (BC) represents a clinical, social, and economic challenge due to tumor-intrinsic characteristics, limitations of diagnostic techniques and a lack of personalized treatments. In the last decade, the use of liquid biopsy has grown as a non-invasive approach to characterize tumors. Moreover, the emergence of omics has increased our knowledge of cancer biology and identified critical BC biomarkers. The rewiring between epigenetics and metabolism has been closely linked to tumor phenotype. Chromatin remodelers interact with each other to control gene silencing in BC, but also with stress-inducible factors or oncogenic signaling cascades to regulate metabolic reprogramming towards glycolysis, the pentose phosphate pathway, and lipogenesis. Concurrently, one-carbon metabolism supplies methyl groups to histone and DNA methyltransferases, leading to the hypermethylation and silencing of suppressor genes in BC. Conversely, α-KG and acetyl-CoA enhance the activity of histone demethylases and acetyl transferases, increasing gene expression, while succinate and fumarate have an inhibitory role. This review is the first to analyze the interplay between epigenome, metabolome and cell signaling pathways in BC, and shows how their regulation contributes to tumor development and progression. Moreover, it summarizes non-invasive biomarkers that could be applied in clinical practice to improve diagnosis, monitoring, prognosis and the therapeutic options in BC.

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“…Bladder cancer (BC) is a frequently occurring and highly recurrent, fatal malignancy of the genitourinary system, the most common of which is bladder urothelial carcinoma (BUC) [4]. The diagnosis and follow-up of bladder cancer mainly rely on cystoscopy and other means, but this kind of examination will bring some pain to patients, and some patients will interrupt the follow-up due to their intolerance [5]. GSDMB has been found to have signi cant expression in a variety of tumors.…”

Section: Introductionmentioning

confidence: 99%

TCGA data mining suggested that high GSDMB expression in bladder cancer indicated an excellent prognosis

Xu¹,

Tang²,

Zhang³

2020

Preprint

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Background. Researchers have demonstrated that GSDMB is highly expressed in cancer tissues and located in amplicons, genomic regions that are often amplified during cancer development. We evaluated the role of GSDMB in bladder cancer using publicly available data.Methods. The relationship between clinical correlation features and GSDMB were analyzed with the Wilcoxon rank sum test (2 groups), Kruskal-Wallis test (multiple groups) and logistic regression. Clinicopathologic characteristics associated with overall survival in TCGA patients using Cox regression and the Kaplan-Meier method. Gene Set Enrichment Analysis (GSEA) was performed using TCGA data set. Results. GSDMB was differentially expressed between the tumor group and the normal group and was highly expressed in the tumor group. Reduced GSDMB expression in BLCA as significantly associated with grade (OR = 4.55, High Grade vs. Low Grade), clinical stage (OR = 2.34, Ⅱvs. Ⅳ), status (OR = 0.51 survival vs. death), all p-values <0.05. Kaplan-Meier survival analysis showed that BLCA with GSDMB- low had a worse prognosis than that with GSDMB-high (p = 0.001). The univariate analysis revealed that GSDMB- low correlated significantly with a poor overall survival (OS) (HR: 0.93; 95%CI: 0.89-0,98; p = 0.006). The multivariate analysis revealed that GSDMB remained independently associated with overall survival, with a HR of 0.711 (CI: 0.55-0.92; p = 0.009). GSEA show that focal adhesion, pathways in cancer, small cell lung cancer, renal cell carcinoma, bladder cancer and other cancer related pathways are differentially enriched in GSDMB low expression phenotype. Conclusions. High GSDMB mRNA expression is an independent risk factor for excellent prognosis in bladder cancer.

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Urinary Metabolic Signatures Detect Recurrences in Non-Muscle Invasive Bladder Cancer

Cited by 20 publications

References 41 publications

The Clinical Experiences of Urine Metabolomics of Genitourinary Urothelial Cancer in a Tertiary Hospital in Taiwan

The Clinical Experiences of Urine Metabolomics of Genitourinary Urothelial Cancer in a Tertiary Hospital in Taiwan

Epigenomic and Metabolomic Integration Reveals Dynamic Metabolic Regulation in Bladder Cancer

TCGA data mining suggested that high GSDMB expression in bladder cancer indicated an excellent prognosis

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