Cancer metabolomic markers in urine: evidence, techniques and recommendations

• Published in: Nature reviews. Urology 2019-06, Vol.16 (6), p.339-362
• Main Authors: Dinges, Sarah S., Hohm, Annika, Vandergrift, Lindsey A., Nowak, Johannes, Habbel, Piet, Kaltashov, Igor A., Cheng, Leo L.
• Format: Article
• Language: English
• Subjects: 631/1647/296; 631/45/535/878; 631/92/320; 692/699/67; Biological markers; Biomarkers; Biomarkers, Tumor - urine; Cancer; Composition; Diagnosis; Early Detection of Cancer - methods; Humans; Identification and classification; Liver Neoplasms - diagnosis; Liver Neoplasms - metabolism; Liver Neoplasms - urine; Male; Mass spectrometry; Medicine; Medicine & Public Health; Metabolites; Metabolome; Metabolomics - methods; Neoplasms - diagnosis; Neoplasms - metabolism; Neoplasms - urine; Oncology, Experimental; Practice Guidelines as Topic; Prostatic Neoplasms - diagnosis; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - urine; Review Article; Scientific imaging; Urine; Urologic Neoplasms - diagnosis; Urologic Neoplasms - metabolism; Urologic Neoplasms - urine; Urology
• ISSN: 1759-4812; 1759-4820
• DOI: 10.1038/s41585-019-0185-3

Urinary tests have been used as noninvasive, cost-effective tools for screening, diagnosis and monitoring of diseases since ancient times. As we progress through the 21st century, modern analytical platforms have enabled effective measurement of metabolites, with promising results for both a deeper understanding of cancer pathophysiology and, ultimately, clinical translation. The first study to measure metabolomic urinary cancer biomarkers using NMR and mass spectrometry (MS) was published in 2006 and, since then, these techniques have been used to detect cancers of the urological system (kidney, prostate and bladder) and nonurological tumours including those of the breast, ovary, lung, liver, gastrointestinal tract, pancreas, bone and blood. This growing field warrants an assessment of the current status of research developments and recommendations to help systematize future research. Urinalysis has long been used as a tool for managing diseases, but 21st century techniques have enabled measurement of metabolomic urinary cancer biomarkers using NMR and mass spectrometry. In this Review, the authors discuss the current status of research developments and offer recommendations to help systematize future research in the field. Key points Initial NMR and mass spectrometry (MS) studies of human urine identified biomarkers that can distinguish patients with cancer from healthy controls and outperform many current clinical markers, possibly enabling early detection. Biomarker panels can be used to identify a single type of cancer, stratify grade and stage, differentiate between multiple cancer types and perform longitudinal evaluations. A similar set of urinary metabolites (hippurate, creatine, tyrosine, citrate, isoleucine, phenylalanine, putrescine, succinate, tryptophan and valine) can indicate malignancy of various organs, possibly reflecting the global metabolic effects of cancer. The lack of specificity means that caution must be exercised and that many biomarkers could be too nonspecific for clinical application. Methodological variations impair comparability of existing studies, highlighting the need for guidelines. The expense of NMR and MS instrumentation means that a centralized testing hub might provide the best solution for eventual clinical implementation of cancer urinary biomarkers.