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

Chao Feng,Liangyu He,Qiuyan Wang,Yuanliang Xie,Xi Wang,Zhong Tang,Yuting Tao,Tianyu Li,Lixin Pan,Shaomei Tang,Zhiyong Lai

doi:10.3389/fgene.2021.695662

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.

Highlights

Bladder cancer (BC) is the 10th most common malignancy worldwide (Bray et al, 2018)
25% of BC patients are diagnosed with muscle-invasive bladder cancer (MIBC), which has a higher rate of relapse and worse prognosis than NMBIC
We accurately classified 12 MIBC patients into basal and luminal subtypes using the BASE47 classifier based on transcriptome expression profiles (Damrauer et al, 2014)

Summary

Introduction

Bladder cancer (BC) is the 10th most common malignancy worldwide (Bray et al, 2018). BC can be classified into nonmuscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) based on the depth of tumor cells invasion (Kamat et al, 2016). 25% of BC patients are diagnosed with MIBC, which has a higher rate of relapse and worse prognosis than NMBIC. Neoadjuvant cisplatin-based chemotherapy (NAC) before radical cystectomy is the standard treatment option for MIBC patients (Grossman et al, 2003; International Collaboration of Trialists et al, 2011). Approximately 40% of MIBC patients benefit from NAC, and only a minority of patients with MIBC respond to immunotherapy (Zargar et al, 2015). New MIBC diagnostic biomarkers and therapeutic strategies are urgently needed

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Conclusion