D'Hue Cedric A, Dhawan Deepika, Peat Tyler, Ramos-Vara José, Jarmusch Alan, Knapp Deborah W, Cooks R Graham
Department of Chemistry, Purdue University, West Lafayette, IN, USA.
Department of Veterinary Clinical Sciences, Purdue University, West Lafayette, IN, USA.
Bladder Cancer. 2018 Jul 30;4(3):283-291. doi: 10.3233/BLC-170125.
In early work ambient ionization mass spectrometry (MS) revealed lipid patterns distinguishing muscle invasive bladder cancer (invasive urothelial carcinoma, InvUC) from normal urothelium. A new ambient ionization MS approach, touch spray MS (TS-MS) can rapidly generate mass spectra in real time, potentially in a point-of-care setting. A tissue sample removed from a patient is touched by a probe, and mass spectra generated within seconds.
To validate TS-MS methods using specimens from naturally-occurring InvUC in dogs where the cancer closely mimics the human condition, and to demonstrate proof-of-concept that TS-MS can elucidate lipid patterns distinguishing InvUC from normal urothelium.
Samples of normal urothelium and InvUC from dogs of several breeds were analyzed by TS-MS with correlative histopathology across each sample. Results were compared to those obtained with desorption electrospray ionization mass spectrometry (DESI-MS), a more traditional method. Data were analyzed by Principal Component Analysis and Linear Discriminant Analysis.
Lipid patterns identified by TS-MS, as well as by DESI-MS, differed between InvUC and normal urothelium with 281.5 (oleic acid) and 563.5 (oleic acid dimer) substantially contributing to the differences. Using histologic diagnosis as the gold standard, TS-MS had a global prediction rate of 93%.
TS-MS can be used to identify lipid patterns that differentiate canine InvUC from normal urothelium. Optimization of TS-MS could lead to a point-of-care approach to distinguish cancer from normal in tissues in real time, and to define biochemical processes leading to cancer development and progression.
在早期研究中,常压电离质谱(MS)揭示了区分肌肉浸润性膀胱癌(浸润性尿路上皮癌,InvUC)与正常尿路上皮的脂质模式。一种新的常压电离质谱方法,即接触喷雾质谱(TS-MS)能够实时快速生成质谱,有可能用于即时检测环境。将从患者身上取下的组织样本与探针接触,数秒内即可生成质谱。
使用犬自然发生的InvUC标本验证TS-MS方法,其中犬的癌症与人类情况极为相似,并证明TS-MS能够阐明区分InvUC与正常尿路上皮的脂质模式的概念验证。
对多个品种犬的正常尿路上皮和InvUC样本进行TS-MS分析,并对每个样本进行相关组织病理学检查。将结果与通过更传统的解吸电喷雾电离质谱(DESI-MS)获得的结果进行比较。通过主成分分析和线性判别分析对数据进行分析。
TS-MS以及DESI-MS识别出的InvUC和正常尿路上皮之间的脂质模式存在差异,其中281.5(油酸)和563.5(油酸二聚体)对差异有显著贡献。以组织学诊断作为金标准,TS-MS的总体预测率为93%。
TS-MS可用于识别区分犬InvUC与正常尿路上皮的脂质模式。优化TS-MS可能会带来一种即时检测方法,能够实时区分组织中的癌症与正常组织,并确定导致癌症发生和发展的生化过程。