Untargeted urinary metabolomics for bladder cancer biomarker screening with ultrahigh-resolution mass spectrometry

Abstract

Bladder cancer (BC) is a common urological malignancy with a high probability of death and recurrence. Cystoscopy is used as a routine examination for diagnosis and following patient monitoring for recurrence. Repeated costly and intrusive treatments may discourage patients from having frequent follow-up screenings. Hence, exploring novel non-invasive ways to help identify recurrent and/or primary BC is critical. In this work, 200 human urine samples were profiled using ultra-high-performance liquid chromatography and ultra-high-resolution mass spectrometry (UHPLC-UHRMS) to uncover molecular markers differentiating BC from non-cancer controls (NCs). Univariate and multivariate statistical analyses with external validation identified metabolites that distinguish BC patients from NCs disease. More detailed divisions for the stage, grade, age, and gender are also discussed. Findings indicate that monitoring urine metabolites may provide a non-invasive and more straightforward diagnostic method for identifying BC and treating recurrent diseases.

Unmasking the Metabolite Signature of Bladder Cancer: A Systematic Review

“…The majority of experimental studies that performed an LC-MS-based analysis included the use of cold organic solvents, such as acetonitrile [ 18 , 22 , 30 , 31 ] or methanol [ 17 , 20 , 23 , 32 ], for deproteinization prior to separation by centrifugation. In addition, metabolite extraction may also include the use of a mixture of solvents, such as acetone and methanol or acetonitrile and methanol [ 22 , 33 , 34 ]. Meanwhile, two studies that performed a GC-MS-based analysis used polydimethylsiloxane/divinylbenzene for the solid-phase microextraction of metabolites [ 35 , 36 ].…”

“…The vast majority of the potential impact of some of these metabolites on BCa development and progression has already been discussed in the present systematic review, particularly in relation to lipids and lipid-like molecules, including FAs (such as linoleic acid, arachidonic acid and myristic acid), suggesting impaired lipid metabolism during BCa development and progression. In addition, oleamide was found to have elevated urinary levels in BCa patients associated with high tumor malignancy and T1 and T2 stage of cancer [ 34 ], as well as in bladder tissue samples from HG-BCa patients [ 106 ]. Oleamide is an endogenous lipid that has previously been demonstrated to exert an effect on Ca 2+ signaling in human BCa cells; that is, it led to an increase in the intracellular content of Ca 2+ in a phospholipase C-independent way [ 108 ].…”

“…↑: increase; ↓: decrease. BCa: bladder cancer; HG: high grade; LG: low grade; NMIBC: non-muscle-invasive bladder cancer; MIBC: muscle-invasive bladder cancer [ 17 , 18 , 19 , 23 , 30 , 33 , 34 , 38 , 39 , 46 , 54 , 60 , 72 , 106 ].…”

A Workflow for Meaningful Interpretation of Classification Results from Handheld Ambient Mass Spectrometry Analysis Probes

“…Oleamide has been reported in honey [ 91 ] and in herbal supplement QC studies [ 92 ], even taking the role of an [accidental] adulterant in several reports. Interestingly, the same ubiquitous oleamide compound has also been observed in untargeted urinary analysis of bladder cancer patients [ 93 ], laryngeal cancer patients [ 94 ], and renal cancer patients [ 95 ], as well as in the serum of patients with colorectal cancer [ 93 , 96 ]. In addition, due to the widespread use of oleamide-containing plasticizers in everyday products, this compound has also been steadily introduced into the human body over the past several years [ 90 ].…”

Multiomics characterization of cell type repertoires for urine liquid biopsies

“…These findings were broadly congruent with prior work characterizing the human urinary metabolomic landscape 30 and offered a static slice of the urinary metabolome. While urine metabolomics are frequently performed for biomarker studies [31][32][33] , a given metabolite can be produced by several different pathways, and metabolomic analyses alone are insufficient for high-resolution insights into underlying pathology.…”