Insight into Fructose-to-Sucrose Ratio as the Potential Target of Urinalysis in Bladder Cancer

Author:

Zhou Dewang1,Huang Jianxu2,Zheng Haoxiang3,Liu Yujun4,Zhu Shimao3,Du Yang1ORCID

Affiliation:

1. Kobilka Institute of Innovative Drug Discovery, School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China

2. Shantou University Medical College, Shantou University, Shantou 515063, China

3. Department of Urology, Medical School, Shenzhen University, Shenzhen 518116, China

4. Medical School, Anhui University of Science and Technology, Huainan 232001, China

Abstract

Bladder cancer usually has been diagnosed in elderly patients as it stays asymptomatic until it presents. Current detection methods for bladder cancer cannot be considered as an adequate screening strategy due to their high invasiveness and low sensitivity. However, there remains uncertainty about targets with high sensitivity and specificity for non-invasive bladder cancer examination. Our study aims to investigate the actionable non-invasive screening biomarkers in bladder cancer. Here, we employed scRNA-seq to explore the crucial biological processes for bladder cancer development. We then utilized bidirectional Mendelian randomization (MR) analysis to explore the bidirectional causal relationship between ATP-associated metabolites in urine and bladder cancer. Lastly, we used a BBN-induced mouse model of bladder cancer to validate the crucial gene identified by scRNA-seq and MR analysis. We found that (1) the ATP metabolism process plays a critical role in bladder cancer development; (2) there is a bidirectional and negative causal relationship between fructose-to-sucrose ratio in urine and the risk of bladder cancer; and (3) the higher expression of TPI1, a critical gene in the fructose metabolism pathway, was validated in BBN-induced bladder tumors. Our results reveal that fructose-to-sucrose ratio can serve as a potential target of urinalysis in bladder cancer.

Funder

National Natural Science Foundation of China Program

Shenzhen Science and Technology Program

Publisher

MDPI AG

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