Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA.
Center for Quantitative Metabolic Research, Cleveland Clinic, Cleveland, OH 44106, USA.
Int J Mol Sci. 2024 Sep 21;25(18):10144. doi: 10.3390/ijms251810144.
Chronic liver diseases, including non-alcoholic fatty liver disease (NAFLD), cirrhosis, and hepatocellular carcinoma (HCC), continue to be a global health burden with a rise in incidence and mortality, necessitating a need for the discovery of novel biomarkers for HCC detection. This study aimed to identify novel non-invasive biomarkers for these different liver disease states. We performed untargeted metabolomics in plasma (Healthy = 9, NAFLD = 14, Cirrhosis = 10, HCC = 34) and saliva samples (Healthy = 9, NAFLD = 14, Cirrhosis = 10, HCC = 22) to test for significant metabolite associations with each disease state. Additionally, we identified enriched biochemical pathways and analyzed correlations of metabolites between, and within, the two biofluids. We identified two salivary metabolites and 28 plasma metabolites significantly associated with at least one liver disease state. No metabolites were significantly correlated between biofluids, but we did identify numerous metabolites correlated within saliva and plasma, respectively. Pathway analysis revealed significant pathways enriched within plasma metabolites for several disease states. Our work provides a detailed analysis of the altered metabolome at various stages of liver disease while providing some context to altered pathways and relationships between metabolites.
慢性肝脏疾病，包括非酒精性脂肪性肝病（NAFLD）、肝硬化和肝细胞癌（HCC），其发病率和死亡率不断上升，仍然是全球健康负担，因此需要发现用于 HCC 检测的新型生物标志物。本研究旨在确定用于这些不同肝脏疾病状态的新型非侵入性生物标志物。我们对血浆（健康=9，NAFLD=14，肝硬化=10，HCC=34）和唾液样本（健康=9，NAFLD=14，肝硬化=10，HCC=22）进行了非靶向代谢组学分析，以测试与每种疾病状态相关的显著代谢物关联。此外，我们还确定了丰富的生化途径，并分析了两种生物流体之间和内部代谢物的相关性。我们确定了两种唾液代谢物和 28 种与至少一种肝脏疾病状态显著相关的血浆代谢物。生物流体之间没有代谢物显著相关，但我们确实分别在唾液和血浆中确定了许多相关的代谢物。途径分析显示，血浆代谢物中与几种疾病状态相关的途径显著富集。我们的工作详细分析了肝脏疾病各个阶段的代谢组变化，并提供了与代谢物途径和相互关系改变有关的背景信息。
