Urinary Metabotyping of Bladder Cancer Using Two-Dimensional Gas Chromatography Time-of-Flight Mass Spectrometry

Abstract

Cystoscopy is the gold standard clinical diagnosis of human bladder cancer (BC). As cystoscopy is expensive and invasive, it compromises patients' compliance toward surveillance screening and challenges the detection of recurrent BC. Therefore, the development of a noninvasive method for the diagnosis and surveillance of BC and the elucidation of BC progression become pertinent. In this study, urine samples from 38 BC patients and 61 non-BC controls were subjected to urinary metabotyping using two-dimensional gas chromatography time-of-flight mass spectrometry (GC×GC-TOFMS). Subsequent to data preprocessing and chemometric analysis, the orthogonal partial least-squares discriminant analysis (OPLS-DA, R2X=0.278, R2Y=0.904 and Q2Y (cumulative)=0.398) model was validated using permutation tests and receiver operating characteristic (ROC) analysis. Marker metabolites were further screened from the OPLS-DA model using statistical tests. GC×GC-TOFMS urinary metabotyping demonstrated 100% specificity and 71% sensitivity in detecting BC, while 100% specificity and 46% sensitivity were observed via cytology. In addition, the model revealed 46 metabolites that characterize human BC. Among the perturbed metabolic pathways, our clinical finding on the alteration of the tryptophan-quinolinic metabolic axis in BC suggested the potential roles of kynurenine in the malignancy and therapy of BC. In conclusion, global urinary metabotyping holds potential for the noninvasive diagnosis and surveillance of BC in clinics. In addition, perturbed metabolic pathways gleaned from urinary metabotyping shed new and established insights on the biology of human BC.

Metabonomic Profiling of Bladder Cancer

“…[138][139][140] In addition to GC/TOFMS, our laboratory applied GC×GC/TOFMS-based metabonomics in profiling BC. 59 The 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 The BC group could be clearly distinguished from the control groups with sensitivity and specificity of 91.3% and 92.5%, respectively. Their model also showed potential in differentiation between muscle-invasive and nonmuscle invasive BC.…”

“…56 Symptomatic controls should also be recruited to avoid confounding factors. 59 In BC metabonomic investigations, baseline characteristics such as stage and grade of tumor, hematuria (gross or micro), surgical interventions and smoking habit should be additionally taken into consideration during the study design. 60 …”

Lipid Metabolism Profiling and Bladder Cancer

“…This study also enabled us to get some tips on the biological events that take place at the high and low-grade bladder tumor carcinogenesis. In another study Pasikanti et al [15] demonstrated down regulation of glycerol in patients with BC compared with non-BC control subjects (Table 1).…”

Nuclear magnetic resonance spectroscopy as a new approach for improvement of early diagnosis and risk stratification of prostate cancer

“…Various studies using mass spectrometric (MS) methods reported promising results for bladder cancer (BCa) detection and separation of invasive BCa from non-invasive BCa (Issaq et al, 2008;Huang et al, 2011;Pasikanti et al, 2013;Chan et al, 2015;Zhou et al, 2016). However, cohort sizes were small in most studies and the effects of renal cancer and bladder inflammation were the major problem in BCa detection (Van et al, 2011).…”