MALDI Mass Spectrometry Imaging of Early- and Late-Stage Serous Ovarian Cancer Tissue Reveals Stage-Specific N-Glycans
MALDI Mass Spectrometry Imaging of Early- and Late-Stage Serous Ovarian Cancer Tissue Reveals Stage-Specific N-Glycans
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DOI：
10.1002/pmic.201800482
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发表时间：
2019-08-16
期刊：
影响因子：
3.4
通讯作者：
Hoffmann, Peter
中科院分区：
文献类型：
--
作者：
Briggs, Matthew T.;Condina, Mark R.;Hoffmann, Peter
上皮性卵巢癌是成年妇女最致命的妇科恶性肿瘤之一。由于对蛋白质N-糖基化的研究已经广泛报道了卵巢癌肿瘤微环境中的异常模式，获得空间信息将揭示卵巢癌发展和进展中的肿瘤特异性N-聚糖改变。基质辅助激光解吸/电离（MALDI）质谱成像（MSI）用于研究来自早期和晚期患者的福尔马林固定石蜡包埋的卵巢癌组织切片上的N-聚糖分布。通过多孔石墨化碳液相色谱-电喷雾电离-串联质谱法（PGC-LC-ESI-MS/MS）鉴定肿瘤特异性N-聚糖并对其结构进行表征，然后将其分配到从MALDI-MSI获得的高分辨率图像。通过MALDI-MSI获得14个N-聚糖的空间分布，并通过LC-MS鉴定和结构表征42个N-聚糖（包括结构和组成异构体）。寡甘露糖、复合中性、二等分和唾液酸化N-聚糖家族的空间分布相对于早期患者定位于晚期卵巢癌患者的肿瘤区域。出现的潜在N-聚糖诊断标志物包括寡聚甘露糖结构（Hex）（6）+（Man）（3）（GlcNAc）（2）和复合中性结构（Hex）（2）（HexNAc）（2）（脱氧己糖）（1）+（Man）（3）（GlcNAc）（2）。这些标志物的分布使用早期和晚期患者的组织微阵列进行评估。
Epithelial ovarian cancer is one of the most fatal gynecological malignancies in adult women. As studies on protein N-glycosylation have extensively reported aberrant patterns in the ovarian cancer tumor microenvironment, obtaining spatial information will uncover tumor-specific N-glycan alterations in ovarian cancer development and progression. matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) is employed to investigate N-glycan distribution on formalin-fixed paraffin-embedded ovarian cancer tissue sections from early- and late-stage patients. Tumor-specific N-glycans are identified and structurally characterized by porous graphitized carbon-liquid chromatography-electrospray ionization-tandem mass spectrometry (PGC-LC-ESI-MS/MS), and then assigned to high-resolution images obtained from MALDI-MSI. Spatial distribution of 14 N-glycans is obtained by MALDI-MSI and 42 N-glycans (including structural and compositional isomers) identified and structurally characterized by LC-MS. The spatial distribution of oligomannose, complex neutral, bisecting, and sialylated N-glycan families are localized to the tumor regions of late-stage ovarian cancer patients relative to early-stage patients. Potential N-glycan diagnostic markers that emerge include the oligomannose structure, (Hex)(6) + (Man)(3)(GlcNAc)(2), and the complex neutral structure, (Hex)(2) (HexNAc)(2) (Deoxyhexose)(1) + (Man)(3)(GlcNAc)(2). The distribution of these markers is evaluated using a tissue microarray of early- and late-stage patients.