Diagnosis of bladder cancer and prediction of survival by urinary metabolomics

Abstract

Bladder cancer (BC) is a common cancer but diagnostic modalities, such as cystoscopy and urinary cytology, have limitations. Here, high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-QTOFMS) was used to profile urine metabolites of 138 patients with BC and 121 control subjects (69 healthy people and 52 patients with hematuria due to non-malignant diseases). Multivariate statistical analysis revealed that the cancer group could be clearly distinguished from the control groups on the basis of their metabolomic profiles, even when the hematuric control group was included. Patients with muscle-invasive BC could also be distinguished from patients with non-muscle-invasive BC on the basis of their metabolomic profiles. Successive analyses identified 12 differential metabolites that contributed to the distinction between the BC and control groups, and many of them turned out to be involved in glycolysis and betaoxidation. The association of these metabolites with cancer was corroborated by microarray results showing that carnitine transferase and pyruvate dehydrogenase complex expressions are significantly altered in cancer groups. In terms of clinical applicability, the differentiation model diagnosed BC with a sensitivity and specificity of 91.3% and 92.5%, respectively, and comparable results were obtained by receiver operating characteristic analysis (AUC = 0.937). Multivariate regression also suggested that the metabolomic profile correlates with cancer-specific survival time. The excellent performance and simplicity of this metabolomics-based approach suggests that it has the potential to augment or even replace the current modalities for BC diagnosis.

Metabolomic analysis identifies differentially produced oral metabolites, including the oncometabolite 2-hydroxyglutarate, in patients with head and neck squamous cell carcinoma

“…However, these investigators did not report the identities of these metabolites. Separate studies have also suggested the association of acylcarnitines with bladder cancer [36], [37], as well as with esophageal squamous cell carcinoma [38]. Since our results also reveal that acylcarnitines are significantly elevated in HNSCC, this class of metabolites may have potential as a biomarker for epithelial-derived cancers.…”

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

“…This result reflected the increased conversion of citrate into fatty acids necessary for β-oxidation to support the rapid proliferation of cancer cells. Numerous disorders have been described that lead to disturbances in energy production and intermediary metabolism, which are characterized by the abnormal levels of acylcarnitines and citrate164142. This also implies a single metabolite will have limited use for an accurate diagnosis of BC, however, the biomarker panel would be more specificity.…”

Investigation of the urinary metabolic variations and the application in bladder cancer biomarker discovery

“…Overall, 33 metabolites had a potentially useful diagnostic value with the AUC above 0.7, and 11 metabolites had a good diagnostic value with the AUC above 0.8 (Supporting Information Table S7). 17 Multivariate ROC curve-based exploratory analysis was carried out (http:// www.metaboanalyst.ca/faces/Secure/upload/RocUploadView. 17 Multivariate ROC curve-based exploratory analysis was carried out (http:// www.metaboanalyst.ca/faces/Secure/upload/RocUploadView.…”

“…12 Although cytology is a noninvasive method and has a high specificity, its sensitivity is not satisfactory, particularly for low-grade tumors. 17 Wittmann BM et al analyzed urine metabolomics of 66 BCa positive samples using UHPLC-MS/MS and GC-MS. Most of the recent research efforts have been directed at discovery of BCa biomarkers using metabolomics technologies.…”