TY - JOUR
T1 - Tumor ratio of unsaturated to saturated sulfatide species is associated with disease-free survival in intrahepatic cholangiocarcinoma
AU - Huizing, L.
AU - Chen, L.
AU - Roeth, A.A.
AU - Heij, L.R.
AU - Flinders, B.
AU - Bouwense, S.A.W.
AU - Balluff, B.
AU - Neumann, U.P.
AU - Heeren, R.M.A.
AU - Damink, S.W.M.O.
AU - Vreeken, R.J.
AU - Schaap, F.G.
N1 - Funding Information:
We are indebted to Cathy van Himbeeck for expert setting-up and management of the local biobank (Maastricht University).
Funding Information:
LC is supported by the Chinese Scholarship Council (Grant No. 201607040063). This research was part of the M4I research program and received financial support from the Dutch Province of Limburg under the LINK program and the Integrated Technology Strategy (ITS) initiative program of Janssen Pharmaceutica NV.
Publisher Copyright:
© 2022, The Author(s).
PY - 2023/6
Y1 - 2023/6
N2 - Purpose Cholangiocarcinoma (CCA) is a malignancy arising from the bile duct epithelium and has a poor outcome. Sulfatides are lipid components of lipid rafts, and are implicated in several cancer types. In the liver, sulfatides are specifically present in the bile ducts. Here, sulfatide abundance and composition were analyzed using mass spectrometry imaging in intrahepatic CCA (iCCA) tumor tissue, and correlated with tumor biology and clinical outcomes.Methods Sulfatides were analyzed in iCCA (n = 17), hepatocellular carcinoma (HCC, n = 10) and colorectal liver metastasis (CRLM, n = 10) tumor samples, as well as tumor-distal samples (control, n = 16) using mass spectrometry imaging. Levels of sulfatides as well as the relative amount in structural classes were compared between groups, and were correlated with clinical outcomes for iCCA patients.Results Sulfatide localization was limited to the respective tumor areas and the bile ducts. Sulfatide abundance was similar in iCCA and control tissue, while intensities were notably higher in CRLM in comparison with control (18-fold, P < 0.05) and HCC tissue (47-fold, P < 0.001). Considerable variation in sulfatide abundance was observed in iCCA tumors. A high ratio of unsaturated to saturated sulfatides was associated with reduced disease-free survival (10 vs. 20 months) in iCCA. The sulfatide pattern in HCC deviated from the other groups, with a higher relative abundance of odd- versus even-chain sulfatides.Conclusion Sulfatides were found in tumor tissue of patients with iCCA, with sulfatide abundance per pixel being similar to bile ducts. In this explorative study, sulfatide abundance was not related to overall survival of iCCA patients. A high ratio of unsaturated to saturated sulfatides was associated with earlier tumor recurrence in patients with iCCA.
AB - Purpose Cholangiocarcinoma (CCA) is a malignancy arising from the bile duct epithelium and has a poor outcome. Sulfatides are lipid components of lipid rafts, and are implicated in several cancer types. In the liver, sulfatides are specifically present in the bile ducts. Here, sulfatide abundance and composition were analyzed using mass spectrometry imaging in intrahepatic CCA (iCCA) tumor tissue, and correlated with tumor biology and clinical outcomes.Methods Sulfatides were analyzed in iCCA (n = 17), hepatocellular carcinoma (HCC, n = 10) and colorectal liver metastasis (CRLM, n = 10) tumor samples, as well as tumor-distal samples (control, n = 16) using mass spectrometry imaging. Levels of sulfatides as well as the relative amount in structural classes were compared between groups, and were correlated with clinical outcomes for iCCA patients.Results Sulfatide localization was limited to the respective tumor areas and the bile ducts. Sulfatide abundance was similar in iCCA and control tissue, while intensities were notably higher in CRLM in comparison with control (18-fold, P < 0.05) and HCC tissue (47-fold, P < 0.001). Considerable variation in sulfatide abundance was observed in iCCA tumors. A high ratio of unsaturated to saturated sulfatides was associated with reduced disease-free survival (10 vs. 20 months) in iCCA. The sulfatide pattern in HCC deviated from the other groups, with a higher relative abundance of odd- versus even-chain sulfatides.Conclusion Sulfatides were found in tumor tissue of patients with iCCA, with sulfatide abundance per pixel being similar to bile ducts. In this explorative study, sulfatide abundance was not related to overall survival of iCCA patients. A high ratio of unsaturated to saturated sulfatides was associated with earlier tumor recurrence in patients with iCCA.
KW - Mass spectrometry imaging
KW - Glycosphingolipids
KW - Cholangiocarcinoma
KW - Colorectal liver metastasis
KW - Hepatocellular carcinoma
KW - Disease-free survival
KW - FATTY-ACID 2-HYDROXYLATION
KW - MECHANISMS
KW - CELLS
U2 - 10.1007/s13402-022-00766-6
DO - 10.1007/s13402-022-00766-6
M3 - Article
C2 - 36630049
SN - 2211-3428
VL - 46
SP - 629
EP - 642
JO - Cellular oncology
JF - Cellular oncology
IS - 3
ER -