Jiang Yingying, Tie Cai, Wang Yang, Bian Dandan, Liu Mei, Wang Ting, Ren Yan, Liu Shuang, Bai Li, Chen Yu, Duan Zhongping, Zheng Sujun, Zhang Jinlan
Difficult and Complicated Liver Diseases and Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, Beijing, China.
Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing Youan Hospital, Capital Medical University, Beijing, China.
Front Oncol. 2020 Sep 8;10:1759. doi: 10.3389/fonc.2020.01759. eCollection 2020.
Serum sphingolipids are widely involved in the development of hepatocellular carcinoma (HCC). We investigated the serum sphingolipid profile in patients with HCC or cirrhosis and explored the potential diagnostic efficiency of serum sphingolipid metabolites which may be helpful in differentiating HCC including α-fetoprotein (AFP)-negative HCC from cirrhosis.
Seventy-two HCC patients (including 24 AFP-negative HCC) and 104 cirrhotic patients were consecutively enrolled in this study. High-performance liquid chromatography-tandem mass spectrometry was used to detect a panel of 57 serum sphingolipid metabolites.
Twenty-four sphingolipid metabolites showed significant differences between HCC and cirrhotic patients (all < 0.05). Sphingosine (d18:1)-1-P was found to have the potential to differentiate HCC from cirrhosis by orthogonal partial least squares discriminant analysis (OPLS-DA). There was no significant difference in the efficacy of Sphingosine (d18:1)-1-P and AFP to distinguish HCC from cirrhosis, and the area under the receiver operating curve (AUC) were 0.85 and 0.83 ( > 0.05), respectively. When the cut-off value of Sphingosine (d18:1)-1-P was set at 56.29 pmol/0.1 ml, the sensitivity and specificity were 79.20% and 78.70%, respectively. Notably, the upregulation of Sphingosine (d18:1)-1-P could also distinguish AFP-negative HCC from cirrhosis with an AUC of 0.79. The sensitivity and specificity were 62.50% and 77.90% at a cut-off value of 56.29 pmol/0.1 ml. Spearman rank correlation analysis revealed that serum Sphingosine (d18:1)-1-P was not correlated with AFP in patients with cirrhosis, AFP-positive HCC, and AFP-negative HCC. Moreover, the difference in the diagnostic efficiency of serum Sphingosine (d18:1)-1-P was not statistically significant between tumor size (≤2 cm vs. >2 cm, = 0.476). Also, there was no difference among patients with different TNM stages and BCLC stages.
The upregulation of serum Sphingosine (d18:1)-1-P exhibits good diagnostic performance for HCC. Particularly, Sphingosine (d18:1)-1-P could also serve as a biomarker for the diagnosis of AFP-negative HCC. These findings may contribute to the non-invasive diagnosis of HCC including AFP-negative HCC.
血清鞘脂广泛参与肝细胞癌（HCC）的发生发展。我们研究了HCC或肝硬化患者的血清鞘脂谱，并探讨了血清鞘脂代谢物的潜在诊断效能，其可能有助于鉴别HCC，包括甲胎蛋白（AFP）阴性的HCC与肝硬化。
本研究连续纳入72例HCC患者（包括24例AFP阴性的HCC患者）和104例肝硬化患者。采用高效液相色谱-串联质谱法检测一组57种血清鞘脂代谢物。
24种鞘脂代谢物在HCC患者和肝硬化患者之间存在显著差异（均P<0.05）。通过正交偏最小二乘法判别分析（OPLS-DA）发现，鞘氨醇（d18:1）-1-P有区分HCC与肝硬化的潜力。鞘氨醇（d18:1）-1-P和AFP区分HCC与肝硬化的效能无显著差异，其受试者工作特征曲线下面积（AUC）分别为0.85和0.83（P>0.05）。当鞘氨醇（d18:1）-1-P的截断值设定为56.29 pmol/0.1 ml时，敏感性和特异性分别为79.20%和78.70%。值得注意的是，鞘氨醇（d18:1）-1-P的上调也能区分AFP阴性的HCC与肝硬化，AUC为0.79。在截断值为56.29 pmol/0.1 ml时，敏感性和特异性分别为62.50%和77.90%。Spearman等级相关分析显示，在肝硬化患者、AFP阳性HCC患者和AFP阴性HCC患者中，血清鞘氨醇（d18:1）-1-P与AFP均无相关性。此外，血清鞘氨醇（d18:1）-1-P的诊断效能在肿瘤大小（≤2 cm与>2 cm，P=0.476）之间无统计学显著差异。不同TNM分期和BCLC分期的患者之间也无差异。
血清鞘氨醇（d18:1）-1-P的上调对HCC具有良好的诊断性能。特别是，鞘氨醇（d18:1）-1-P也可作为诊断AFP阴性HCC的生物标志物。这些发现可能有助于HCC包括AFP阴性HCC的非侵入性诊断。
