Three serum metabolite signatures for diagnosing low-grade and high-grade bladder cancer

Abstract

To address the shortcomings of cystoscopy and urine cytology for detecting and grading bladder cancer (BC), ultrahigh performance liquid chromatography (UHPLC) coupled with Q-TOF mass spectrometry in conjunction with univariate and multivariate statistical analyses was employed as an alternative method for the diagnosis of BC. A series of differential serum metabolites were further identified for low-grade(LG) and high-grade(HG) BC patients, suggesting metabolic dysfunction in malignant proliferation, immune escape, differentiation, apoptosis and invasion of cancer cells in BC patients. In total, three serum metabolites including inosine, acetyl-N-formyl-5-methoxykynurenamine and PS(O-18:0/0:0) were selected by binary logistic regression analysis, and receiver operating characteristic (ROC) test based on their combined use for HG BC showed that the area under the curve (AUC) was 0.961 in the discovery set and 0.950 in the validation set when compared to LG BC. Likewise, this composite biomarker panel can also differentiate LG BC from healthy controls with the AUC of 0.993 and 0.991 in the discovery and validation set, respectively. This finding suggested that this composite serum metabolite signature was a promising and less invasive classifier for probing and grading BC, which deserved to be further investigated in larger samples.

Bladder cancer recurrence surveillance by urine metabolomics analysis

“…Phenylalanine, arginine, proline and tryptophan pathways were found significantly altered ( p -value < 0.05). This observation was in agreement with recent results 26 reporting increased levels of four tryptophan metabolites (kynurenine, acetyl-N-formyl-5-methoxykynurenamine, indoleacetic acid and indolelactic acid) in serum samples of BC patients compared to healthy controls, and previous studies in BC tissue 9 and urine 12 that suggested the potential role of kynurenine in the malignancy BC associated to IDO and IDO2, two tryptophan-metabolizing enzymes that control the tryptophan catabolism-signaling pathway. The generation of kynurenine and other tryptophan metabolites can modulate T-cell immunity via activation of suppressive regulatory T-cells and activation of aryl hydrocarbon receptor, thus promoting cancer cell survival 27 .…”

“…Phenylacetylglutamine is synthesized in the liver from glutamine and phenylacetyl-CoA and is a dosing biomarker for patients with urea cycle disorders; it is also a known microbial metabolite 31 . Altered levels of phenylacetylglutamine might indicate a deregulation of the phenylalanine or glutamine metabolism as well, as observed in a previous urinary metabolomic study involving BC patients and healthy controls that attributed this deregulation to the increased energy demands of cancer cells for growing and proliferation 26 . Urinary citrate is a normal component in urine and the major inhibitor of kidney stone formation.…”

Vnn1 pantetheinase limits the Warburg effect and sarcoma growth by rescuing mitochondrial activity

“…Metabolomics analysis combining liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) approaches segregated R from VR tumors ( Fig 2C and D ) and highlighted metabolic pathways associated with cell growth in R tumors. Some among these were recently shown to be a source of biomarkers for cancer progression ( Mimmi et al, 2013 ; Buzatto et al, 2017 ; Di Virgilio & Adinolfi, 2017 ; Tan et al, 2017 ). NMR analysis further identified the presence of excess lactate and saturated/unsaturated fatty acids in R tumors, whereas VR tumors were enriched in glucose and glutathione ( Fig 2D ), VdR tumors showing an R tumor–like profile ( Fig S2C and D ).…”

Analysis of the Metabolic Characteristics of Serum Samples in Patients With Multiple Myeloma

“…Relative to invasive detection methods such as puncture or biopsy of bone marrow, the ideal biomarker in clinical diagnosis of newly-diagnosed MM (NDMM) patients and the monitoring of relapsed MM (RMM) should possess optimal sensitivity and specificity in samples obtained from patients in a minimally-invasive manner, such as blood or saliva. The mounting evidence demonstrate that metabolomic profiling methods might be feasible for identifying diagnostic or prognostic biomarkers for patients with solid tumors and hematologic malignancies, including colorectal cancer, bladder cancer, acute myeloid leukemia and acute lymphoblastic leukemia (Bannur et al, 2014 ; Chen et al, 2014 ; Liu et al, 2017 ; Tan et al, 2017 ). Metabolomics is the quantitative measurement of all low-molecular-weight metabolites in an organism under specific environmental conditions, representing the end products of cellular processes (Jordan et al, 2009 ).…”