AUTHOR=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 TITLE=Upregulation of Serum Sphingosine (d18:1)-1-P Potentially Contributes to Distinguish HCC Including AFP-Negative HCC From Cirrhosis JOURNAL=Frontiers in Oncology VOLUME=10 YEAR=2020 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.01759 DOI=10.3389/fonc.2020.01759 ISSN=2234-943X ABSTRACT=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 in differentiating HCC including α-fetoprotein (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 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). 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 (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 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, P = 0.476). Also, there was no difference among patients with different TNM stages and BCLC stages.

Conclusion

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.