Integrative Transcriptomic, Lipidomic, and Metabolomic Analysis Reveals Potential Biomarkers of Basal and Luminal Muscle Invasive Bladder Cancer Subtypes

Abstract

Muscle invasive bladder cancer (MIBC) is a heterogeneous disease with a high recurrence rate and poor clinical outcomes. Molecular subtype provides a new framework for the study of MIBC heterogeneity. Clinically, MIBC can be classified as basal and luminal subtypes; they display different clinical and pathological characteristics, but the molecular mechanism is still unclear. Lipidomic and metabolomic molecules have recently been considered to play an important role in the genesis and development of tumors, especially as potential biomarkers. Their different expression profiles in basal and luminal subtypes provide clues for the molecular mechanism of basal and luminal subtypes and the discovery of new biomarkers. Herein, we stratified MIBC patients into basal and luminal subtypes using a MIBC classifier based on transcriptome expression profiles. We qualitatively and quantitatively analyzed the lipids and metabolites of basal and luminal MIBC subtypes and identified their differential lipid and metabolite profiles. Our results suggest that free fatty acids (FFAs) and sulfatides (SLs), which are closely associated with immune and stromal cell types, can contribute to the diagnosis of basal and luminal subtypes of MIBC. Moreover, we showed that glycerophosphocholine (GCP)/imidazoles and nucleosides/imidazoles ratios can accurately distinguish the basal and luminal tumors. Overall, by integrating transcriptomic, lipidomic, and metabolomic data, our study reveals specific biomarkers to differentially diagnose basal and luminal MIBC subtypes and may provide a basis for precision therapy of MIBC.

Unmasking the Metabolite Signature of Bladder Cancer: A Systematic Review

“…In addition, one of the most abundant lipid species found in tumor tissue-derived samples was PE and, more precisely, PE (32:1). Notably, this lipid was equally found in the previously mentioned experimental studies regarding tissue-derived samples, in which it was upregulated in HG-BCa-related studies and downregulated in the comparison between distinct MIBC molecular subtypes [ 38 , 39 , 106 ]. This suggests that this phospholipid may be a potential biomarker in BCa detection, especially in the high-grade state of the disease, excluding the basal molecular subtype.…”

“…To achieve this goal, they used an LC-MS-based approach to identify and quantify metabolites in 12 tissue samples of MIBC. Their results revealed 73 altered metabolites in the basal and luminal MIBC subtypes, suggesting that sulfatides (SLs), SMs and free FAs mainly contribute to the diagnosis of the basal MIBC subtype, while PCs and PEs are typically more abundant in the luminal subtype [ 39 ]. Thus, these metabolites may be useful to provide an improved differential diagnosis of MIBC.…”

“…↑: increase; ↓: decrease. BCa: bladder cancer; HG: high grade; LG: low grade; NMIBC: non-muscle-invasive bladder cancer; MIBC: muscle-invasive bladder cancer [ 17 , 18 , 19 , 23 , 30 , 33 , 34 , 38 , 39 , 46 , 54 , 60 , 72 , 106 ].…”

Multiomics Approaches Identify Biomarkers for BAT Thermogenesis

“…10 Utilizing a multiomics approach of integrative transcriptomics, lipidomics, and metabolomics reveals potential biomarkers to distinguish basal and luminal muscle-invasive bladder cancer subtypes. 11 Recently, the entire lipidome combined with transcriptomics analysis reveals the WAT heterogeneity between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) involved in lipolysis, lipogenesis, inflammatory response, and thermogenesis. 12 Comprehensive lipidomics analysis has been performed to investigate the browning heterogeneity of VAT and SAT by β3-adrenergic stimulation and reveals the dramatic alteration of glycerophospholipids and sphingolipids in VAT rather than in SAT.…”

“…Among them, lipidomics analysis serves as a powerful tool for understanding the biochemical and cellular mechanisms by detecting and monitoring the change of various arrays of lipid species, while transcriptomics examines genome-wide RNA levels, both qualitatively and quantitatively . Utilizing a multiomics approach of integrative transcriptomics, lipidomics, and metabolomics reveals potential biomarkers to distinguish basal and luminal muscle-invasive bladder cancer subtypes . Recently, the entire lipidome combined with transcriptomics analysis reveals the WAT heterogeneity between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) involved in lipolysis, lipogenesis, inflammatory response, and thermogenesis .…”