Multi-omics Integration Analysis Robustly Predicts High-Grade Patient Survival and Identifies CPT1B Effect on Fatty Acid Metabolism in Bladder Cancer

Abstract

Purpose: The perturbation of metabolic pathways in high-grade bladder cancer has not been investigated. We aimed to identify a metabolic signature in high-grade bladder cancer by integrating unbiased metabolomics, lipidomics, and transcriptomics to predict patient survival and to discover novel therapeutic targets. Experimental Design: We performed high-resolution liquid chromatography mass spectrometry (LC-MS) and bioinformatic analysis to determine the global metabolome and lipidome in high-grade bladder cancer. We further investigated the effects of impaired metabolic pathways using in vitro and in vivo models. Results: We identified 519 differential metabolites and 19 lipids that were differentially expressed between low-grade and high-grade bladder cancer using the NIST MS metabolomics compendium and lipidblast MS/MS libraries, respectively. Pathway analysis revealed a unique set of biochemical pathways that are highly deregulated in high-grade bladder cancer. Integromics analysis identified a molecular gene signature associated with poor patient survival in bladder cancer. Low expression of CPT1B in high-grade tumors was associated with low FAO and low acyl carnitine levels in high-grade bladder cancer, which were confirmed using tissue microarrays. Ectopic expression of the CPT1B in high-grade bladder cancer cells led to reduced EMT in in vitro, and reduced cell proliferation, EMT, and metastasis in vivo. Conclusions: Our study demonstrates a novel approach for the integration of metabolomics, lipidomics, and transcriptomics data, and identifies a common gene signature associated with poor survival in patients with bladder cancer. Our data also suggest that impairment of FAO due to downregulation of CPT1B plays an important role in the progression toward high-grade bladder cancer and provide potential targets for therapeutic intervention.

Dysregulated Gut Homeostasis Observed Prior to the Accumulation of the Brain Amyloid-β in Tg2576 Mice

“…Changes in circulating vitamin B12 were examined by mass spectrometry. Vitamin B12 was extracted from plasma using liquid-liquid extraction as described in earlier publications [91][92][93]. The HPLC column used was Zorbax eclipse XDB C-18, 1.8 micron, 4.6 × 100 mm Agilent technologies Santa Clara, CA, USA).…”

Bioinformatics combined with quantitative proteomics analyses and identification of potential biomarkers in cholangiocarcinoma

“…Fortunately, as bioinformatics has continued developing and public databases such as GEO and TCGA have been established, the realization of combined multiomics applications has become more acceptable. By sharing transcriptome microarray data uploaded by experimenters around the world, we can apply combinations of multiple omics techniques to provide a comprehensive and systematic perspective to advance the understanding of the molecular mechanism of CCA [25][26][27].…”

Vertical and horizontal integration of multi-omics data with miodin

“…Multi-omics experiments are indispensable for studying biological systems across molecular layers and tools for performing data analysis are actively being developed (42)(43)(44)(45). One outstanding challenge in multi-omics data integration and analysis is to combine several tools into a coherent pipeline, which is time-consuming and requires extensive technical knowledge of various data types and platforms.…”