Sphingomyelin (30:1; O2) as a novel lipid biomarker associated with the diagnosis of intrahepatic cholangiocarcinoma

Background Intrahepatic cholangiocarcinoma (ICC) is a primary hepatic malignancy with an incidence second only to hepatocellular carcinoma (HCC). Preoperative differentiation between ICC and HCC remains challenging in certain cases. This study aimed to identify potential diagnostic lipid biomarkers for ICC. Methods Untargeted lipidomic analysis was performed on plasma samples from 50 normal controls (NC), 50 patients with HCC, and 30 patients with ICC. Results The results showed that the differential lipid species in the plasma of ICC patients, compared to NC group, were predominantly phosphatidylethanolamine (PE), sphingomyelin (SM), and ceramide (Cer), whereas HCC patients primarily exhibited differences in phosphatidylcholine (PC), triglyceride (TG), and acylcarnitine (CAR). Notably, relative to the NC group, SM (30:1; O2) was significantly upregulated in the ICC group but downregulated in the HCC group ( P  < 0.05). Compared with conventional tumor markers such as carbohydrate antigen 19 − 9 (CA19-9) and carcinoembryonic antigen (CEA), SM (30:1; O2) demonstrated superior diagnostic efficacy for ICC (AUC = 0.8793, P  < 0.001). Correlation analysis showed that SM (30:1; O2) levels were significantly positively correlated with ICC TNM stage (ρ = 0.721, P  < 0.001), indicating a potential association with tumor progression. Conclusions SM (30:1; O2) is a promising biomarker for ICC diagnosis, capable of effectively distinguishing ICC from HCC, and providing valuable guidance for preoperative diagnosis and therapeutic decision-making.