Maastricht Multimodal Molecular Imaging Institute (M4I), Maastricht University, Universiteitssingel 50, 6229 ER, Maastricht, The Netherlands.
Department 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.
Cell Oncol (Dordr). 2023 Jun;46(3):629-642. doi: 10.1007/s13402-022-00766-6. Epub 2023 Jan 11.
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.
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.
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.
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.
胆管癌（CCA）是一种起源于胆管上皮的恶性肿瘤，预后不良。硫酸酯是脂筏的脂质成分，与多种癌症类型有关。在肝脏中，硫酸酯特异性存在于胆管中。在这里，使用质谱成像分析了肝内 CCA（iCCA）肿瘤组织中的硫酸酯丰度和组成，并将其与肿瘤生物学和临床结果相关联。
使用质谱成像分析了 iCCA（n=17）、肝细胞癌（HCC，n=10）和结直肠癌肝转移（CRLM，n=10）肿瘤样本以及肿瘤远端样本（对照，n=16）中的硫酸酯。比较了各组之间硫酸酯的水平及其结构类别中的相对含量，并与 iCCA 患者的临床结果相关联。
硫酸酯的定位仅限于各自的肿瘤区域和胆管。iCCA 和对照组织中的硫酸酯丰度相似，而 CRLM 与对照组织（18 倍，P<0.05）和 HCC 组织（47 倍，P<0.001）相比，强度明显更高。在 iCCA 肿瘤中观察到硫酸酯丰度的显著变化。不饱和硫酸酯与饱和硫酸酯的高比值与 iCCA 患者无疾病生存时间缩短（10 个月 vs. 20 个月）相关。HCC 的硫酸酯模式与其他组不同，奇数链硫酸酯的相对丰度较高。
在 iCCA 患者的肿瘤组织中发现了硫酸酯，每个像素的硫酸酯丰度与胆管相似。在这项探索性研究中，硫酸酯丰度与 iCCA 患者的总生存无关。不饱和硫酸酯与饱和硫酸酯的高比值与 iCCA 患者的肿瘤早期复发相关。
