Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China.
Department of Pharmacy, Peking University People's Hospital, Beijing, China.
Front Endocrinol (Lausanne). 2022 Jan 26;12:816748. doi: 10.3389/fendo.2021.816748. eCollection 2021.
Metabolic syndrome (MetS) is an independent risk factor for hepatocellular cancer (HCC). Currently, there is no highly sensitive and specific biomarkers for HCC surveillance in MetS population. Metabolomics has been reported as a powerful technology for biomarker discovery. In the present study, we aimed to explore novel biomarkers with high sensitivity and specificity for MetS-positive [MetS(+)] HCC by metabolomic analysis. At first, many serum metabolites were found dysregulated in MetS(+) HCC individuals. Validation of the dysregulated metabolites by targeted metabolite analyses revealed that serum L-glutamic acid (L-glu), pipecolic acid (PA) and 7-methylguanine (7-mG) were increased in MetS(+) HCC compared to MetS group. Then a biomarker panel including L-glu, PA and alpha-fetoprotein (AFP) was identified as a novel biomarker for the diagnosis of MetS(+) HCC. Receiver operating characteristic (ROC) curve was drawn and the area under the ROC curve (AUC) was 0.87 for discriminating MetS(+) HCC from MetS group. The biomarker panel was capable of detecting small (AUC = 0.82) and early-stage (AUC = 0.78) tumors as well. Moreover, it exhibited great diagnostic performance (AUC = 0.93) for discriminating MetS(+) HCC from other MetS-associated cancers, including colorectal cancer and gastric cancer. Collectively, our study establishes a novel diagnostic tool for MetS(+) HCC.
代谢综合征（MetS）是肝细胞癌（HCC）的独立危险因素。目前，在 MetS 人群中，尚无用于 HCC 监测的高度敏感和特异的生物标志物。代谢组学已被报道为一种用于发现生物标志物的强大技术。在本研究中，我们旨在通过代谢组学分析探索用于 MetS 阳性 [MetS(+)] HCC 的具有高灵敏度和特异性的新型生物标志物。首先，在 MetS(+) HCC 个体中发现许多血清代谢物失调。通过靶向代谢物分析对失调代谢物的验证表明，与 MetS 组相比，血清 L-谷氨酸（L-glu）、哌可酸（PA）和 7-甲基鸟嘌呤（7-mG）在 MetS(+) HCC 中增加。然后，包括 L-glu、PA 和甲胎蛋白（AFP）在内的生物标志物组合被确定为诊断 MetS(+) HCC 的新型生物标志物。绘制了受试者工作特征（ROC）曲线，ROC 曲线下面积（AUC）为 0.87，用于区分 MetS(+) HCC 和 MetS 组。该生物标志物组合能够检测到小（AUC = 0.82）和早期（AUC = 0.78）肿瘤。此外，它在区分 MetS(+) HCC 与其他 MetS 相关癌症（包括结直肠癌和胃癌）方面表现出出色的诊断性能（AUC = 0.93）。总之，我们的研究为 MetS(+) HCC 建立了一种新的诊断工具。
