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N-Glycan profiling of lung adenocarcinoma in patients at different stages of disease.
Modern Pathology ( IF 7.1 ) Pub Date : 2020-01-06 , DOI: 10.1038/s41379-019-0441-3 Erika Lattová 1 , Jana Skřičková 2 , Jitka Hausnerová 3 , Lukáš Frola 3 , Leoš Křen 3 , Ivana Ihnatová 4 , Zbyněk Zdráhal 1, 5 , Joseph Bryant 6 , Mikuláš Popovič 6
Modern Pathology ( IF 7.1 ) Pub Date : 2020-01-06 , DOI: 10.1038/s41379-019-0441-3 Erika Lattová 1 , Jana Skřičková 2 , Jitka Hausnerová 3 , Lukáš Frola 3 , Leoš Křen 3 , Ivana Ihnatová 4 , Zbyněk Zdráhal 1, 5 , Joseph Bryant 6 , Mikuláš Popovič 6
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Lung adenocarcinoma (LAC) is the most common form of lung cancer that increases in non-smokers at younger age. Altered protein glycosylation is one of the hallmarks of malignancy, its role in cancer progression is still poorly understood. In this study, we report mass spectrometric (MS) analysis of N-glycans released from fresh or defrosted tissue specimens from 24 patients with LAC. Comparison of cancerous versus adjacent healthy tissues revealed substantial differences in N-glycan profiles associated with disease. The significant increase in paucimannose and high-mannose glycans with 6-9 mannose residues and decline in the sialylated complex biantenary core fucosylated glycan with composition NeuAcGal2GlcNAc2Man3GlcNAc2Fuc were general features of tumors. In addition, 42 new N-glycan compositions were detected in cancerous tissues. The prominent changes in advanced disease stages were mostly observed in core fucosylated N-glycans with additional fucose (Fuc) residue/s and enhanced branching with non-galactosylated N-acetyl-glucosamine (GlcNAc) units. Both of these monosaccharide types were linked preferably on the 6-antenna. Importantly, as compared with noncancerous tissues, a number of these significant changes were clearly detectable early on in stage I. Application of N-glycan data obtained from tissues was next assessed and validated for evaluation of small sized biopsies obtained via bronchoscopy. In summary, observed alterations and data of newly detected N-glycans expand knowledge about the glycosylation in LAC and may contribute to research in more tailored therapies. Moreover, the results demonstrate effectiveness of the presented approach for utility in rapid discrimination of cancerous from healthy lung tissues.
中文翻译：
不同疾病阶段患者肺腺癌的 N-聚糖分析。
肺腺癌 (LAC) 是最常见的肺癌形式，在年轻的非吸烟者中发病率增加。改变的蛋白质糖基化是恶性肿瘤的标志之一，其在癌症进展中的作用仍知之甚少。在这项研究中，我们报告了从 24 名 LAC 患者的新鲜或解冻组织标本中释放的 N-聚糖的质谱 (MS) 分析。癌组织与邻近健康组织的比较揭示了与疾病相关的 N-聚糖谱的显着差异。具有 6-9 个甘露糖残基的寡甘露糖和高甘露糖聚糖的显着增加以及组成为 NeuAcGal2GlcNAc2Man3GlcNAc2Fuc 的唾液酸化复合双臂核心岩藻糖基化聚糖的减少是肿瘤的一般特征。此外，在癌组织中检测到 42 种新的 N-聚糖成分。晚期疾病阶段的显着变化主要在具有额外岩藻糖 (Fuc) 残基和非半乳糖基化 N-乙酰氨基葡萄糖 (GlcNAc) 单元的增强分支的核心岩藻糖基化 N-聚糖中观察到。这两种单糖类型都优选连接在 6 天线上。重要的是，与非癌性组织相比，许多这些显着变化在 I 阶段的早期就可以清楚地检测到。接下来评估和验证从组织中获得的 N-聚糖数据的应用，以评估通过支气管镜检查获得的小型活组织检查。总之，观察到的变化和新检测到的 N-聚糖的数据扩展了关于 LAC 中糖基化的知识，并可能有助于研究更多定制疗法。而且，
更新日期：2020-01-06
中文翻译：
不同疾病阶段患者肺腺癌的 N-聚糖分析。
肺腺癌 (LAC) 是最常见的肺癌形式，在年轻的非吸烟者中发病率增加。改变的蛋白质糖基化是恶性肿瘤的标志之一，其在癌症进展中的作用仍知之甚少。在这项研究中，我们报告了从 24 名 LAC 患者的新鲜或解冻组织标本中释放的 N-聚糖的质谱 (MS) 分析。癌组织与邻近健康组织的比较揭示了与疾病相关的 N-聚糖谱的显着差异。具有 6-9 个甘露糖残基的寡甘露糖和高甘露糖聚糖的显着增加以及组成为 NeuAcGal2GlcNAc2Man3GlcNAc2Fuc 的唾液酸化复合双臂核心岩藻糖基化聚糖的减少是肿瘤的一般特征。此外，在癌组织中检测到 42 种新的 N-聚糖成分。晚期疾病阶段的显着变化主要在具有额外岩藻糖 (Fuc) 残基和非半乳糖基化 N-乙酰氨基葡萄糖 (GlcNAc) 单元的增强分支的核心岩藻糖基化 N-聚糖中观察到。这两种单糖类型都优选连接在 6 天线上。重要的是，与非癌性组织相比，许多这些显着变化在 I 阶段的早期就可以清楚地检测到。接下来评估和验证从组织中获得的 N-聚糖数据的应用，以评估通过支气管镜检查获得的小型活组织检查。总之，观察到的变化和新检测到的 N-聚糖的数据扩展了关于 LAC 中糖基化的知识，并可能有助于研究更多定制疗法。而且，
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