Le Faouder Julie, Laouirem Samira, Alexandrov Theodore, Ben-Harzallah Soundes, Léger Thibaut, Albuquerque Miguel, Bedossa Pierre, Paradis Valérie
Claude Bernard Institute, Paris-Diderot University, Paris, France; INSERM U773, Biomedical Research Center, Paris-Diderot University, Paris, France.
Proteomics. 2014 Apr;14(7-8):965-72. doi: 10.1002/pmic.201300463.
Cholangiocarcinoma (CC) is the second most common primary malignancy of the liver. Although all CC derive from biliary epithelial cells, two main subtypes, hilar (H), and peripheral (P) CC are described. The objective of the study was to compare, using MALDI imaging mass spectrometry (MALDI IMS), in situ proteomic profiles of H- and P-CC in order to assess whether these subtypes may express different markers and to describe their respective localizations. Twenty-seven CC (16 P-CC and 11 H-CC) were subjected to MALDI IMS. Proteomic data were submitted to a dedicated cross-classification comparative design, enabling comparison of the entire generated spectra. Immunohistochemistry was performed for validation. Comparative analysis yielded a list of 19 differential protein peaks for the two subtypes, 14 of which were overexpressed in H-CC and five in P-CC. Among H-CC protein markers, most discriminant were human neutrophil peptides 1-3 that were expressed mainly by tumor cells and S100 proteins (A6 and A11) that were restricted to the stromal area. In P-CC, thymosin β4 was diffusely overexpressed. These results highlight the potential of MALDI IMS to discover new relevant biomarkers of CC and to characterize the heterogeneity of the two different subtypes.
胆管癌（CC）是肝脏第二常见的原发性恶性肿瘤。尽管所有CC均起源于胆管上皮细胞，但可分为两种主要亚型，即肝门部（H）和周围型（P）CC。本研究的目的是使用基质辅助激光解吸电离成像质谱（MALDI IMS）比较H-CC和P-CC的原位蛋白质组图谱，以评估这些亚型是否可能表达不同的标志物并描述其各自的定位。对27例CC（16例P-CC和11例H-CC）进行了MALDI IMS检测。蛋白质组数据采用专门的交叉分类比较设计，以便对整个生成的光谱进行比较。采用免疫组织化学进行验证。比较分析得出了两种亚型的19个差异蛋白峰列表，其中14个在H-CC中过表达，5个在P-CC中过表达。在H-CC蛋白标志物中，最具鉴别力的是主要由肿瘤细胞表达的人中性粒细胞肽1-3和局限于基质区域的S100蛋白（A6和A11）。在P-CC中，胸腺素β4广泛过表达。这些结果突出了MALDI IMS在发现CC新的相关生物标志物以及表征两种不同亚型异质性方面的潜力。
