Lu Haiyan, Zhang Hua, Xiao Yipo, Chingin Konstantin, Dai Chao, Wei Feng, Wang Nanya, Frankevich Vladimir, Chagovets Vitaly, Zhou Fan, Chen Huanwen
State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, Changchun 130012, P. R. China.
Analyst. 2020 Oct 21;145(20):6470-6477. doi: 10.1039/d0an01080d. Epub 2020 Aug 28.
Comparative studies of molecular alterations upon cancer between mice and humans are of great importance in order to determine the relevance of research involving mouse cancer models to the development of diagnostic and therapeutic approaches in clinical practice as well as for the mechanistic studies of pathology in humans. Herein, using molecular fingerprinting by internal extractive electrospray ionization mass spectrometry (iEESI-MS), we identified 50 differential signals in mouse liver tissue and 62 differential signals in human liver tissue that undergo significant intensity alterations (variable importance in the project (VIP) >1.0) upon liver cancer, out of which only 27 were common in both mouse and human tissues. Out of the 27 common differential signals, six types of phospholipids were also identified to undergo significant alterations in human serum upon liver cancer, including PC(34:2), PC(36:4), PC(38:6), PC(36:2), PC(38:4) and PC(42:9). Statistical analysis of the relative intensity distribution of these six identified phospholipids in serum allowed confident determination of liver cancer in humans (sensitivity 91.0%, specificity 88.0%, and accuracy 90.0%). Our results indicate that, despite the significant difference in the overall alterations of phospholipid profiles upon liver cancer between humans and mice, the six identified 'core' differential phospholipids of liver cancer found in the liver tissues of both humans and mice as well as in human serum show high potential as a minimal panel for the rapid targeted diagnosis of liver cancer with high accuracy, sensitivity and specificity using direct mass spectrometry (MS) analysis.
为了确定涉及小鼠癌症模型的研究与临床实践中诊断和治疗方法的开发以及人类病理学机制研究的相关性,对小鼠和人类癌症发生时的分子改变进行比较研究具有重要意义。在此,我们使用内萃取电喷雾电离质谱(iEESI-MS)进行分子指纹识别,在小鼠肝脏组织中鉴定出50个差异信号,在人类肝脏组织中鉴定出62个差异信号,这些信号在肝癌发生时强度发生显著改变(项目中的变量重要性(VIP)>1.0),其中只有27个在小鼠和人类组织中是共同的。在这27个共同的差异信号中,还鉴定出六种磷脂在人类肝癌患者血清中也发生了显著改变,包括PC(34:2)、PC(36:4)、PC(38:6)、PC(36:2)、PC(38:4)和PC(42:9)。对血清中这六种已鉴定磷脂的相对强度分布进行统计分析,可以可靠地诊断人类肝癌(灵敏度91.0%,特异性88.0%,准确性90.0%)。我们的结果表明,尽管人类和小鼠肝癌发生时磷脂谱的总体变化存在显著差异,但在人类和小鼠肝脏组织以及人类血清中发现的六种已鉴定的肝癌“核心”差异磷脂,作为一个最小的检测组,具有通过直接质谱(MS)分析以高精度、高灵敏度和高特异性快速靶向诊断肝癌的巨大潜力。