Integrative Metabolomic and Transcriptomic Analysis for the Study of Bladder Cancer

Abstract

Metabolism reprogramming is considered a hallmark of cancer. The study of bladder cancer (BC) metabolism could be the key to developing new strategies for diagnosis and therapy. This work aimed to identify tissue and urinary metabolic signatures as biomarkers of BC and get further insight into BC tumor biology through the study of gene-metabolite networks and the integration of metabolomics and transcriptomics data. BC and control tissue samples (n = 44) from the same patients were analyzed by High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance and microarrays techniques. Besides, urinary profiling study (n = 35) was performed in the same patients to identify a metabolomic profile, linked with BC tissue hallmarks, as a potential non-invasive approach for BC diagnosis. The metabolic profile allowed for the classification of BC tissue samples with a sensitivity and specificity of 100%. The most discriminant metabolites for BC tissue samples reflected alterations in amino acids, glutathione, and taurine metabolic pathways. Transcriptomic data supported metabolomic results and revealed a predominant downregulation of metabolic genes belonging to phosphorylative oxidation, tricarboxylic acid cycle, and amino acid metabolism. The urinary profiling study showed a relation with taurine and other amino acids perturbed pathways observed in BC tissue samples, and classified BC from non-tumor urine samples with good sensitivities (91%) and specificities (77%). This urinary profile could be used as a non-invasive tool for BC diagnosis and follow-up.

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

“…Urine is in contact with BC tumors and so the biochemical composition of the urine samples might be modified by molecules released from BC cells. This hypothesis is supported by recent preliminary results obtained by liquid chromatography–MS [24] that suggest the use of urinary biomarkers not only for BC detection, but also for patient monitoring during surveillance.…”

“…The latest advances in mass spectrometry (MS) and nuclear magnetic resonance (NMR), as well as in data analysis strategies, have fostered the use of metabolomics in this area of research [13,18]. In the context of BC, NMR and MS studies have focused on the identification of biomarkers for BC diagnosis or monitoring using urine and blood [19,20,21,22,23,24]. These studies have obtained good sensitivities and specificities (≈80–100%) comparing tumor versus health samples [25] and have shown taurine, citrate, and amino acid altered metabolism, among others, linked with BC.…”

Traditional Classification and Novel Subtyping Systems for Bladder Cancer

“…With the rapid development of sequencing, mass spectrometry and other techniques, studies based on genomics and transcriptome (17), epigenetics (18), proteomics (19) and other omics (20)(21)(22) will provide a new direction for the accurate diagnosis and treatment of bladder cancer. A good classification system should meet the following criteria: I.…”

Internal cross-linked polymeric nanoparticles with dual sensitivity for combination therapy of muscle-invasive bladder cancer

“…In addition, GSH is involved in the excretion of chemotherapy drugs from tumor cells, resulting in a decrease in drug accumulation in tumor cells. It is also worth highlighting the correlations between GSH levels and aggressiveness of bladder cancer cells [15]. Therefore, GSH plays an important role in the resistance to chemotherapy of bladder cancer.…”