NMR-Based Prostate Cancer Metabolomics

Author's accepted version (postprint).This is an Accepted Manuscript of an article published by Springer in Methods in Molecular Biology on 22 May 2018.Available online: https://doi.org/10.1007/978-1-4939-7845-8_14acceptedVersio

Identification and validation of leucine-rich α-2-glycoprotein 1 as a noninvasive biomarker for improved precision in prostate cancer risk stratification

Background: More accurate risk assessments are needed to improve prostate cancer management. Objective: To identify blood-based protein biomarkers that provided prognostic information for risk stratification. Design, Setting, and Participants: Mass spectrometry was used to identify biomarker candidates from blood, and validation studies were performed in four independent cohorts retrospectively collected between 1988 and 2015. Outcome Measurements and Statistical Analysis: The primary outcome objectives were progression-free survival, prostate cancer–specific survival (PCSS), and overall survival. Statistical analyses to assess survival and model performance were performed. Results and Limitation: Serum leucine-rich α-2-glycoprotein 1 (LRG1) was found to be elevated in fatal prostate cancer. LRG1 provided prognostic information independent of metastasis and increased the accuracy in predicting PCSS, particularly in the first 3 yr. A high LRG1 level is associated with an average of two-fold higher risk of disease-progression and mortality in both high-risk and metastatic patients. However, our study design, with a retrospective analysis of samples spanning several decades back, limits the assessment of the clinical utility of LRG1 in today’s clinical practice. Thus, independent prospective studies are needed to establish LRG1 as a clinically useful biomarker for patient management. Conclusions: High blood levels of LRG1 are unfavourable in newly diagnosed high-risk and metastatic prostate cancer, and LRG1 increased the accuracy of risk stratification of prostate cancer patients. Patient Summary: High blood levels of leucine-rich α-2-glycoprotein 1 are unfavourable in newly diagnosed high-risk and metastatic prostate cancer.</p

NMR-Based Prostate Cancer Metabolomics

Prostate cancer is the second most common malignancy, and the fifth leading cause of cancer-related death among men, worldwide. A major unsolved clinical challenge in prostate cancer is the ability to accurately distinguish indolent cancer types from the aggressive ones. Reprogramming of metabolism is now a widely accepted hallmark of cancer development, where cancer cells must be able to convert nutrients to biomass while maintaining energy production. Metabolomics is the large-scale study of small molecules, commonly known as metabolites, within cells, biofluids, tissues, or organisms. Nuclear magnetic resonance (NMR) spectroscopy is commonly applied in metabolomics studies of cancer. This chapter provides protocols for NMR-based metabolomics of cell cultures, biofluids (serum and urine), and intact tissue, with concurrent advice for optimal biobanking and sample preparation procedures

NMR-Based Prostate Cancer Metabolomics

Prostate cancer is the second most common malignancy, and the fifth leading cause of cancer-related death among men, worldwide. A major unsolved clinical challenge in prostate cancer is the ability to accurately distinguish indolent cancer types from the aggressive ones. Reprogramming of metabolism is now a widely accepted hallmark of cancer development, where cancer cells must be able to convert nutrients to biomass while maintaining energy production. Metabolomics is the large-scale study of small molecules, commonly known as metabolites, within cells, biofluids, tissues, or organisms. Nuclear magnetic resonance (NMR) spectroscopy is commonly applied in metabolomics studies of cancer. This chapter provides protocols for NMR-based metabolomics of cell cultures, biofluids (serum and urine), and intact tissue, with concurrent advice for optimal biobanking and sample preparation procedures