肺癌相关唾液蛋白中半乳糖化n -聚糖的糖组学研究

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2023-05-01 DOI:10.1002/prca.202200012
Fan Zhang, Mingyuan Xie, Zhen Tang, Hailong Xie, Lixin Yue, Xilong Wang, Jiajun Yang, Yanhua Chen, Zheng Li
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引用次数: 0

摘要

目的:肺癌(LC)是世界范围内癌症相关死亡的主要原因,主要是由于诊断晚和预后差。唾液是发现生物标志物的重要来源,含有丰富的生物信息。本研究的目的是确定唾液蛋白的半乳糖基化水平是否与LC相关。实验设计:首先,我们利用凝集素芯片分析了5组(健康志愿者[HV]: 28,良性肺部疾病[BPD]: 27,肺腺癌[ADC]: 39,鳞状细胞癌[SCC]: 28,小细胞肺癌[SCLC]: 22) 144份唾液样本中单纯斑野鸭凝集素I (BS-I)识别的糖型的变化。随后通过凝集素印迹技术对每组的合并样本进行验证。最后,采用MALDI-TOF/TOF-MS分析各组唾液糖蛋白的n -聚糖谱。结果:与BPD和HV相比,LC患者中被BS-I识别的半乳糖基化聚糖的表达水平明显升高。受试者工作特征(ROC)分析显示,BS-I识别的唾液糖型水平能够鉴别肺部疾病(BPD、ADC、SCC和SCLC)和HV, AUC为0.700 (95% CI: 0.589-0.812),鉴别LC和BPD的AUC为0.860 (95% CI: 0.763-0.956)。与HV(30.1%)和BPD(33.7%)相比,ADC(38.4%)、SCC(43.1%)和SCLC(39.5%)中半乳糖化n -聚糖的比例也有所增加,而且只有LC组(ADC、SCC和SCLC)中才有两个半乳糖化n -聚糖峰(m/z 1828.683、2418.853)。结论和临床意义:这些发现可以提供与LC相关的半乳糖化n -聚糖的重要信息,并促进基于唾液中半乳糖化n -聚糖精确改变的LC生物标志物的研究。
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Integrated glycomics strategy for galactosylated-N-glycans recognized by Bandeiraea Simplicifolia Lectin I in salivary proteins associated with lung cancer.

Purpose: Lung cancer (LC) is the leading cause of cancer-related deaths worldwide, mainly due to late diagnosis and poor prognosis. Saliva is an important source for discovering biomarkers and contains an abundance of biological information. The purpose of this study was to determine whether galactosylation levels of salivary proteins are associated with LC.

Experimental design: First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. Pooled samples from each group were subsequently validated by the lectin blotting technique. Finally, the N-glycan profiles of their salivary glycoproteins isolated by the BS-I-magnetic particle conjugates from pooled samples for each group were analyzed by MALDI-TOF/TOF-MS.

Results: The results showed that the expression level of galactosylated glycans recognized by BS-I was significantly increased in patients with LC compared with BPD and HV. Receiver operating characteristic (ROC) analysis indicated that the levels of salivary glycopattern recognized by BS-I could discriminate lung disease (BPD, ADC, SCC, and SCLC) and HV with an AUC of 0.700 (95% CI: 0.589-0.812), and discriminate LC and BPD with an AUC of 0.860 (95% CI: 0.763-0.956). Also, the proportion of galactosylated N-glycans in ADC (38.4%), SCC (43.1%), and SCLC (39.5%) increased compared to HV (30.1%) and BPD (33.7%), and two galactosylated N-glycan peaks (m/z 1828.683, 2418.853) could be identified only in the LC groups (ADC, SCC, and SCLC).

Conclusions and clinical relevance: These findings could provide crucial information on galactosylated N-linked glycans associated with LC and facilitate the study of LC biomarkers based on precise alterations of galactosylated N-glycans in saliva.

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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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