Tumor ratio of unsaturated to saturated sulfatide species is associated with disease-free survival in intrahepatic cholangiocarcinoma

Cellular Oncology · 12 authors, 4 centres

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A high ratio of unsaturated to saturated sulfatide species was associated with shorter disease-free survival in intrahepatic cholangiocarcinoma patients.

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Sulfatide localization was limited to tumor areas and bile ducts. Sulfatide abundance per pixel was similar in iCCA and control tissue, while CRLM showed markedly higher intensities compared with control (18-fold) and HCC tissue (47-fold). Considerable inter-tumor variation in total sulfatide intensity was observed in iCCA. No correlation was found between total sulfatide intensity and overall or disease-free survival or tumor biology in iCCA. A high ratio of unsaturated to saturated sulfatide species was associated with reduced disease-free survival (10 vs. 20 months) in iCCA. The HCC sulfatide pattern differed from other groups, with higher relative abundance of odd-chain species. This explorative study has a small sample size, and the molecular mechanisms linking sulfatide saturation index to tumor recurrence remain unclear.

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cohort

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oncology

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ORIGINAL PAPER

PMC10205872

Tumor ratio of unsaturated to saturated sulfatide species is associated with disease-free survival in intrahepatic cholangiocarcinoma

Cellular Oncology

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ABSTRACT

Abstract 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. Supplementary Information The online version contains supplementary material available at 10.1007/s13402-022-00766-6. Keywords: Mass spectrometry imaging, Glycosphingolipids, Cholangiocarcinoma, Colorectal liver metastasis, Hepatocellular carcinoma, Disease-free survival

CITATION EXPORT

Lennart Huizing, Lin Chen, Anjali A Roeth et al.. Tumor ratio of unsaturated to saturated sulfatide species is associated with disease-free survival in intrahepatic cholangiocarcinoma. Cellular Oncology. (2023). https://doi.org/10.1007/s13402-022-00766-6

AUTHORS

12 · 4 CENTRES

Lennart Huizing, Lin Chen, Anjali A Roeth, Lara R Heij, Bryn Flinders, Stefan A W Bouwense, Benjamin Balluff, Ulf P Neumann, Ron M A Heeren, Steven W M Olde Damink, Rob J Vreeken, Frank G Schaap

1Maastricht Multimodal Molecular Imaging Institute (M4I), Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands
2Department of Surgery, Maastricht University Medical Center and NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, PO BOX 616, 6200 MD Maastricht, The Netherlands
3Department of General, Visceral and Transplantation Surgery, RWTH University Hospital Aachen, Aachen, Germany
4Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium