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N-Glycan profiling of lung adenocarcinoma in patients at different stages of disease.

不同疾病阶段患者肺腺癌的 N-聚糖谱。

  • 影响因子:6.13
  • DOI:10.1038/s41379-019-0441-3
  • 作者列表:"Lattová E","Skřičková J","Hausnerová J","Frola L","Křen L","Ihnatová I","Zdráhal Z","Bryant J","Popovič M
  • 发表时间:2020-01-06
Abstract

: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.

摘要

: 肺腺癌 (LAC) 是最常见的肺癌形式,在不吸烟者年轻时增加。改变的蛋白质糖基化是恶性肿瘤的标志之一,它在癌症进展中的作用仍然知之甚少。在这项研究中,我们报告了 24 例 LAC 患者新鲜或解冻组织标本释放的 N-聚糖的质谱 (MS) 分析。癌症与邻近健康组织的比较揭示了与疾病相关的 N-聚糖谱的实质性差异。具有 6-9 个甘露糖残基的低甘露糖和高甘露糖聚糖的显著增加和具有组成 NeuAcGal2GlcNAc2Man3GlcNAc2Fuc 的唾液酸化复合物生物触角核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。疾病晚期的显著变化主要见于核心岩藻糖基化的 N-聚糖,具有额外的岩藻糖 (Fuc) 残基/s 和非半乳糖基化的 N-乙酰氨基葡萄糖 (GlcNAc) 的增强分支单位。这两种单糖类型最好在 6 天线上连接。重要的是,与非癌组织相比,这些显著的变化中的一些在 I 期早期就被清楚地检测到。接下来应用从组织中获得的 N-聚糖数据进行评估和验证,以评价通过支气管镜获得的小尺寸活检。总之,观察到的新检测到的 N-聚糖的改变和数据扩展了关于 LAC 中糖基化的知识,可能有助于更量身定制疗法的研究。此外,结果证明了所提出的方法在快速区分癌症和健康肺组织方面的有效性。

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影响因子:1.84
发表时间:2020-01-01
来源期刊:Oncology letters
DOI:10.3892/ol.2019.11149
作者列表:["Das SK","Huang YY","Li B","Yu XX","Xiao RH","Yang HF"]

METHODS::The aim of the present study was to compare the safety and efficacy of cryoablation (CA) and microwave ablation (MWA) as treatments for non-small cell lung cancer (NSCLC). Patients with stage IIIB or IV NSCLC treated with CA (n=45) or MWA (n=56) were enrolled in the present study. The primary endpoint was progression-free survival (PFS); the secondary endpoints included overall survival (OS) time and adverse events (AEs). The median PFS times between the two groups were not significantly different (P=0.36): CA, 10 months [95% confidence interval (CI), 7.5-12.4] vs. MWA, 11 months (95% CI, 9.5-12.4). The OS times between the two groups were also not significantly different (P=0.07): CA, 27.5 months (95% CI, 22.8-31.2 months) vs. MWA, 18 months (95% CI, 12.5-23.5). For larger tumors (>3 cm), patients treated with MWA had significantly longer median PFS (P=0.04; MWA, 10.5 months vs. CA, 7.0 months) and OS times (P=0.04; MWA, 24.5 months vs. CA, 14.5 months) compared patients treated with CA. However, for smaller tumors (≤3 cm), median PFS (P=0.79; MWA, 11.0 months vs. CA, 13.0 months) and OS times (P=0.39; MWA, 30.0 months vs. CA, 26.5 months) between the two groups did not differ significantly. The incidence rates of AEs were similar in the two groups (P>0.05). The number of applicators, tumor size and length of the lung traversed by applicators were associated with a higher risk of pneumothorax and intra-pulmonary hemorrhage in the two groups. Treatment with CA resulted in significantly less intraprocedural pain compared with treatment with MWA (P=0.001). Overall, the present study demonstrated that CA and MWA were comparably safe and effective procedures for the treatment of small tumors. However, treatment with MWA was superior compared with CA for the treatment of large tumors.

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