Cellular Oncology ( IF 4.9 ) Pub Date : 2023-01-11 , DOI: 10.1007/s13402-022-00766-6
Lennart Huizing 1 , Lin Chen 2 , Anjali A Roeth 2, 3 , Lara R Heij 3 , Bryn Flinders 1 , Stefan A W Bouwense 2 , Benjamin Balluff 1 , Ulf P Neumann 2, 3 , Ron M A Heeren 1 , Steven W M Olde Damink 2, 3 , Rob J Vreeken 1, 4 , Frank G Schaap 2, 3
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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.
中文翻译:
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不饱和与饱和硫苷脂种类的肿瘤比率与肝内胆管癌的无病生存相关
目的
胆管癌 (CCA) 是一种起源于胆管上皮细胞的恶性肿瘤,预后很差。硫苷脂是脂筏的脂质成分,与多种癌症类型有关。在肝脏中,硫苷脂特别存在于胆管中。在这里,使用质谱成像分析肝内 CCA (iCCA) 肿瘤组织中的硫苷脂丰度和组成,并与肿瘤生物学和临床结果相关联。
方法
使用质量分析 iCCA(n = 17)、肝细胞癌(HCC,n = 10)和结直肠肝转移(CRLM,n = 10)肿瘤样本以及肿瘤远端样本(对照,n = 16)中的硫苷脂光谱成像。在各组之间比较硫苷脂水平以及结构类别中的相对量,并与 iCCA 患者的临床结果相关。
结果
硫苷定位限于各自的肿瘤区域和胆管。iCCA 和对照组织中的硫苷脂丰度相似,而 CRLM 中的强度明显高于对照(18 倍,P < 0.05)和 HCC 组织(47 倍,P < 0.001)。在 iCCA 肿瘤中观察到硫苷脂丰度的相当大的变化。iCCA 中不饱和硫苷与饱和硫苷的高比例与无病生存率降低(10 个月与 20 个月)有关。HCC 中的硫苷脂模式与其他组不同,奇数链硫苷脂与偶数链硫苷脂的相对丰度更高。
结论
在 iCCA 患者的肿瘤组织中发现了硫苷脂,每个像素的硫苷脂丰度与胆管相似。在这项探索性研究中,硫苷脂丰度与 iCCA 患者的总生存期无关。不饱和与饱和硫苷脂的高比例与 iCCA 患者的早期肿瘤复发相关。