LC-MS-Based Plasma Metabolomics and Lipidomics Analyses for Differential Diagnosis of Bladder Cancer and Renal Cell Carcinoma.

Xiang Liu,Zhigang Ji,Xiaoyue Tang,Xiaoyan Liu,Zhengguang Guo,Jing Li,Xiangming Cheng,Yushi Zhang,Haidan Sun,Zhan Wang,Wei Sun,Mingxin Zhang

doi:10.3389/fonc.2020.00717

Abstract

Bladder cancer (BC) and Renal cell carcinoma(RCC) are the two most frequent genitourinary cancers in China. In this study, a comprehensive liquid chromatography—mass spectrometry (LC-MS) based method, which utilizes both plasma metabolomics and lipidomics platform, has been carried out to discriminate the global plasma profiles of 64 patients with BC, 74 patients with RCC, and 141 healthy controls. Apparent separation was observed between cancer (BC and RCC) plasma samples and controls. The area under the receiving operator characteristic curve (AUC) was 0.985 and 0.993 by plasma metabolomics and lipidomics, respectively (external validation group: AUC was 0.944 and 0.976, respectively). Combined plasma metabolomics and lipidomics showed good predictive ability with an AUC of 1 (external validation group: AUC = 0.99). Then, separation was observed between the BC and RCC samples. The AUC was 0.862, 0.853 and 0.939, respectively, by plasma metabolomics, lipidomics and combined metabolomics and lipidomics (external validation group: AUC was 0.802, 0.898, and 0.942, respectively). Furthermore, we also found eight metabolites that showed good predictive ability for BC, RCC and control discrimination. This study indicated that plasma metabolomics and lipidomics may be effective for BC, RCC and control discrimination, and combined plasma metabolomics and lipidomics showed better predictive performance. This study would provide a reference for BC and RCC biomarker discovery, not only for early detection and screening, but also for differential diagnosis.

Highlights

Bladder cancer (BC) and Renal cell carcinoma(RCC) are, respectively, the second and third most common genitourinary cancers in Europe and North America, and the first two most commonly occurring genitourinary cancers in China [1]
liquid chromatography— mass spectrometry (LC-MS) based plasma metabolomics and lipidomics were performed based on 95 healthy controls, 42 patients with BC and 53 patients with RCC
We have for the first time utilized data from a combination of plasma metabolomics and lipidomics analysis for BC and RCC early detection and screening, and provided a new insight into the differential diagnosis of BC and RCC

Summary

Introduction

Bladder cancer (BC) and Renal cell carcinoma(RCC) are, respectively, the second and third most common genitourinary cancers in Europe and North America, and the first two most commonly occurring genitourinary cancers in China [1]. Cystoscopy may fail to visualize certain areas within the bladder, and may fail to detect some cancers, cases of carcinoma in situ [2]. Developing convenient and novel techniques for early detection of BC and RCC with high sensitivity and specificity is urgently required. There are increasing numbers of studies evaluating the use of metabolomic analyses in the diagnosis of a number of pathologies [6,7,8] and in the elucidation of the clinical pathogenesis of various diseases [9, 10]. Lipidomics is an emerging independent branch of metabolomics [11], and lipid metabolism dysfunction has been found to be associated with the pathogenesis of many diseases, such as ovarian cancer [12], prostate cancer [13], and breast cancer [14], among others

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Conclusion