Integrative Multi-Omics Analysis for the Determination of Non-Muscle Invasive vs. Muscle Invasive Bladder Cancer: A Pilot Study.

Evan Yi-Wen Yu, Hao Zhang, Yuanqing Fu, Ya-Ting Chen, Qiu-Yi Tang, Yu-Xiang Liu, Yan-Xi Zhang, Shi-Zhi Wang, Anke Wesselius, Wen-Chao Li, Maurice P Zeegers, Bin Xu

Journal: Current oncology (Toronto, Ont.) 2022;29(8):5442-5456

PMID: 36005168

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Abstract

OBJECTIVES

The molecular landscape of non-muscle-invasive (NMIBC) and muscle-invasive (MIBC) bladder cancer based on molecular characteristics is essential but poorly understood. In this pilot study we aimed to identify a multi-omics signature that can distinguish MIBC from NMIBC. Such a signature can assist in finding potential mechanistic biomarkers and druggable targets.

METHODS

Patients diagnosed with NMIBC ( = 15) and MIBC ( = 11) were recruited at a tertiary-care hospital in Nanjing from 1 April 2021, and 31 July 2021. Blood, urine and stool samples per participant were collected, in which the serum metabolome, urine metabolome, gut microbiome, and serum extracellular vesicles (EV) proteome were quantified. The differences of the global profiles and individual omics measure between NMIBC vs. MIBC were assessed by permutational multivariate analysis and the Mann-Whitney test, respectively. Logistic regression analysis was used to assess the association of each identified analyte with NMIBC vs. MIBC, and the Spearman correlation was used to investigate the correlations between identified analytes, where both were adjusted for age, sex and smoking status.

RESULTS

Among 3168 multi-omics measures that passed the quality control, 159 were identified to be differentiated in NMIBC vs. MIBC. Of these, 46 analytes were associated with bladder cancer progression. In addition, the global profiles showed significantly different urine metabolome ( = 0.029), gut microbiome ( = 0.036), and serum EV (extracellular vesicles) proteome ( = 0.039) but not serum metabolome ( = 0.059). We also observed 17 (35%) analytes that had been developed as drug targets. Multiple interactions were obtained between the identified analytes, whereas for the majority (61%), the number of interactions was at 11-20. Moreover, unconjugated bilirubin ( = 0.009) and white blood cell count ( = 0.006) were also shown to be different in NMIBC and MIBC, and associated with 11 identified omics analytes.

CONCLUSIONS

The pilot study has shown promising to monitor the progression of bladder cancer by integrating multi-omics data and deserves further investigations.

Address: Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Epidemiology & Biostatistics, School of Public Health, Southeast University, Nanjing 210009, China.; Department of Epidemiology, CAPHRI Care and Public Health Research Institute, Maastricht University, 6229 ER Maastricht, The Netherlands.; State Key Laboratory of Bioelectronics, National Demonstration Center for Experimental Biomedical Engineering Education, Southeast University, Nanjing 210096, China.; Nanjing EVLiXiR Biotechnology Co., Ltd., Nanjing 210032, China.; Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou 310024, China.; Westlake Intelligent Biomarker Discovery Laboratory, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310024, China.; Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou 310024, China.; Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Epidemiology & Biostatistics, School of Public Health, Southeast University, Nanjing 210009, China.; Medical School of Southeast University, Nanjing 210009, China.; Key Laboratory of Environmental Medicine Engineering, School of Public Health, Southeast University, Ministry of Education, Nanjing 210009, China.; Department of Epidemiology, CAPHRI Care and Public Health Research Institute, Maastricht University, 6229 ER Maastricht, The Netherlands.; School of Nutrition and Translational Research in Metabolism, Maastricht University, 6229 ER Maastricht, The Netherlands.; Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing 210009, China.

DOI: 10.3390/curroncol29080430

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Medical:

https://medlineplus.gov/bladdercancer.html

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https://assays.cancer.gov/CPTAC-1595

MeSH Terms: Humans, Pilot Projects, Prognosis, Proteome, Urinary Bladder Neoplasms