Zhongshan Hospital Institute for Clinical Science, Shanghai Institute of Clinical Bioinformatics, Shanghai Engineering Research for AI Technology for Cardiopulmonary Diseases, Fudan University, Shanghai, China.
Department of Respiratory Diseases, Clinical Center for Molecular Diagnosis and Therapy, The Second Hospital of Fujian Medical University, Quanzhou, Fujian Province, China.
Cancer Lett. 2020 Feb 1;470:75-83. doi: 10.1016/j.canlet.2019.08.014. Epub 2019 Oct 23.
Disordered lipid metabolisms have been evidenced in lung cancer as well as its subtypes. Lipidomics with in-depth mining is considered as a critical member of the multiple omics family and a lipid-specific tool to understand disease-associated lipid metabolism and disease-specific dysfunctions of lipid species, discover biomarkers and targets for monitoring therapeutic strategies, and provide insights into lipid profiling and pathophysiological mechanisms in lung cancer. The present review describes the characters and patterns of lipidomic profiles in patients with different lung cancer subtypes, important values of comprehensive lipidomic profiles in understanding of lung cancer heterogeneity, urgent needs of standardized methodologies, potential mechanisms by lipid-associated enzymes and proteins, and the importance of integration between clinical phenomes and lipidomic profiles. The characteristics of lipidomic profiles in different lung cancer subtypes are extremely varied among study designs, objects, methods, and analyses. Preliminary data from recent studies demonstrate the specificity of lipidomic profiles specific for lung cancer stage, severity, subtype, and response to drugs. The heterogeneity of lipidomic profiles and lipid metabolism may be part of systems heterogeneity in lung cancer and be responsible for the development of drug resistance, although there are needs for direct evidence to show the existence of intra- or inter-lung cancer heterogeneity of lipidomic profiles. With an increasing understanding of expression profiles of genes and proteins, lipidomic profiles should be associated with activities of enzymes and proteins involved in the processes of lipid metabolism, which can be profiled with genomics and proteomics, and to provide the opportunity for the integration of lipidomic profiles with gene and protein expression profiles. The concept of clinical trans-omics should be emphasized to integrate data of lipidomics with clinical phenomics to identify disease-specific and phenome-specific biomarkers and targets, although there are still a large number of challenges to be overcome in the integration between clinical phenomes and lipidomic profiles.
脂质代谢紊乱在肺癌及其亚型中已有证据。脂质组学与深入挖掘被认为是多种组学家族的重要成员,也是了解与疾病相关的脂质代谢和脂质物种疾病特异性功能障碍、发现生物标志物和监测治疗策略的靶点、深入了解肺癌中脂质谱和病理生理机制的脂质特异性工具。本综述描述了不同肺癌亚型患者的脂质组学特征和模式、综合脂质组学在理解肺癌异质性中的重要价值、标准化方法的迫切需求、脂质相关酶和蛋白质的潜在机制以及临床表型和脂质组学之间整合的重要性。不同肺癌亚型的脂质组学特征在研究设计、对象、方法和分析上存在极大的差异。来自最近研究的初步数据表明,脂质组学特征对肺癌分期、严重程度、亚型和对药物的反应具有特异性。脂质组学特征和脂质代谢的异质性可能是肺癌系统异质性的一部分,可能导致耐药性的产生,尽管需要直接证据来证明脂质组学特征在肺癌内部或之间的异质性的存在。随着对基因和蛋白质表达谱认识的不断深入,脂质组学特征应该与参与脂质代谢过程的酶和蛋白质的活性相关联,可以通过基因组学和蛋白质组学来进行分析,并为将脂质组学特征与基因和蛋白质表达谱进行整合提供机会。应该强调临床跨组学的概念,将脂质组学数据与临床表型学数据整合,以识别疾病特异性和表型特异性的生物标志物和靶点,尽管在临床表型学和脂质组学特征之间进行整合仍然存在许多挑战。