Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, Fisciano, SA, Italy.
Innovative Immunological Models Unit, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale", 80131, Naples, Italy.
J Transl Med. 2023 Dec 18;21(1):918. doi: 10.1186/s12967-023-04801-4.
Early diagnosis of hepatocellular carcinoma (HCC) is essential towards the improvement of prognosis and patient survival. Circulating markers such as α-fetoprotein (AFP) and micro-RNAs represent useful tools but still have limitations. Identifying new markers can be fundamental to improve both diagnosis and prognosis. In this approach, we harness the potential of metabolomics and lipidomics to uncover potential signatures of HCC.
A combined untargeted metabolomics and lipidomics plasma profiling of 102 HCV-positive patients was performed by HILIC and RP-UHPLC coupled to Mass Spectrometry. Biochemical parameters of liver function (AST, ALT, GGT) and liver cancer biomarkers (AFP, CA19.9 e CEA) were evaluated by standard assays.
HCC was characterized by an elevation of short and long-chain acylcarnitines, asymmetric dimethylarginine, methylguanine, isoleucylproline and a global reduction of lysophosphatidylcholines. A supervised PLS-DA model showed that the predictive accuracy for HCC class of metabolomics and lipidomics was superior to AFP for the test set (100.00% and 94.40% vs 55.00%). Additionally, the model was applied to HCC patients with AFP values < 20 ng/mL, and, by using only the top 20 variables selected by VIP scores achieved an Area Under Curve (AUC) performance of 0.94.
These exploratory findings highlight how metabo-lipidomics enables the distinction of HCC from chronic HCV conditions. The identified biomarkers have high diagnostic potential and could represent a viable tool to support and assist in HCC diagnosis, including AFP-negative patients.
早期诊断肝细胞癌 (HCC) 对于改善预后和患者生存至关重要。α-胎蛋白 (AFP) 和 microRNAs 等循环标志物是有用的工具，但仍存在局限性。鉴定新的标志物对于改善诊断和预后都非常重要。在本研究中，我们利用代谢组学和脂质组学的潜力来发现 HCC 的潜在标志物。
对 102 例 HCV 阳性患者进行了非靶向代谢组学和脂质组学联合分析，采用亲水相互作用色谱法 (HILIC) 和反相超高效液相色谱法 (RP-UHPLC) 与质谱联用。采用标准方法测定肝功能生化参数 (AST、ALT、GGT) 和肝癌标志物 (AFP、CA19.9 和 CEA)。
HCC 患者的短链和长链酰基肉碱、不对称二甲基精氨酸、甲基鸟嘌呤、异亮氨酸脯氨酸水平升高，而溶血磷脂酰胆碱水平降低。偏最小二乘判别分析 (PLS-DA) 模型显示，代谢组学和脂质组学对 HCC 类别的预测准确性优于 AFP（测试集为 100.00%和 94.40% vs 55.00%）。此外，该模型还应用于 AFP 值<20ng/mL 的 HCC 患者，仅使用 VIP 得分选择的前 20 个变量，曲线下面积 (AUC) 性能为 0.94。
这些探索性发现强调了代谢脂质组学如何能够区分 HCC 与慢性 HCV 状况。所鉴定的生物标志物具有很高的诊断潜力，可能成为支持和辅助 HCC 诊断的有效工具，包括 AFP 阴性患者。
