Upregulation of Serum Sphingosine (d18:1)-1-P Potentially Contributes to Distinguish HCC Including AFP-Negative HCC From Cirrhosis

Background: 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 to differentiating HCC including AFP negative HCC from cirrhosis. Methods: 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 (HPLC-MS/MS) was used to detect a panel of 57 serum sphingolipid metabolites. Results: Twenty-four sphingolipid metabolites showed significant differences between HCC and cirrhotic patients (All P 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 up-regulation of Sphingosine (d18:1)-1-P could also distinguish AFP negative HCC from cirrhosis with the 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 (≤ 2cm vs >2cm, P = 0.476). Also there was no difference among patients with different TNM stages and BCLC stages. Conclusions: The up-regulation 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.