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

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

doi:10.3389/fgene.2021.695662

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

Front Genet. 2021 Aug 16:12:695662. doi: 10.3389/fgene.2021.695662. eCollection 2021.

Authors

Chao Feng^{1

2

3}, Lixin Pan^{1

2

3}, Shaomei Tang^{2

4}, Liangyu He^{5

1

6

2}, Xi Wang^{1

2}, Yuting Tao^{1

2

3}, Yuanliang Xie^{1

2

7}, Zhiyong Lai^{1

2}, Zhong Tang⁸, Qiuyan Wang^{1

2}, Tianyu Li^{5

1

6

2}

Affiliations

¹ Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Nanning, China.
² Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Nanning, China.
³ Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, China.
⁴ Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
⁵ Institute of Urology and Nephrology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
⁶ Department of Urology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
⁷ Department of Urology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China.
⁸ School of Information and Management, Guangxi Medical University, Nanning, China.

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.

Keywords: MIBC; lipidomics; metabolomic; subtype; transcriptomic.