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菲律宾肺癌及瘤周组织的糖组学、糖蛋白质组学和蛋白质组学分析:I-III期患者的病例系列研究

Glycomic, Glycoproteomic, and Proteomic Profiling of Philippine Lung Cancer and Peritumoral Tissues: Case Series Study of Patients Stages I-III.

作者信息

Alvarez Michael Russelle, Zhou Qingwen, Tena Jennyfer, Barboza Mariana, Wong Maurice, Xie Yixuan, Lebrilla Carlito B, Cabanatan Michelle, Barzaga Ma Teresa, Tan-Liu Nelia, Heralde Francisco M, Serrano Luster, Nacario Ruel C, Completo Gladys Cherisse

机构信息

Department of Chemistry, University of California Davis, Davis, CA 95616, USA.

Institute of Chemistry, University of the Philippines Los Baños, Laguna 4031, Philippines.

出版信息

Cancers (Basel). 2023 Mar 2;15(5):1559. doi: 10.3390/cancers15051559.

Abstract

Lung cancer is the leading cause of cancer death and non-small cell lung carcinoma (NSCLC) accounting for majority of lung cancers. Thus, it is important to find potential biomarkers, such as glycans and glycoproteins, which can be used as diagnostic tools against NSCLC. Here, the N-glycome, proteome, and N-glycosylation distribution maps of tumor and peritumoral tissues of Filipino lung cancer patients (n = 5) were characterized. We present several case studies with varying stages of cancer development (I-III), mutation status (), and biomarker expression based on a three-gene panel (, , and ). Although the profiles of each patient were unique, specific trends arose that correlated with the role of aberrant glycosylation in cancer progression. Specifically, we observed a general increase in the relative abundance of high-mannose and sialofucosylated N-glycans in tumor samples. Analysis of the glycan distribution per glycosite revealed that these sialofucosylated N-glycans were specifically attached to glycoproteins involved in key cellular processes, including metabolism, cell adhesion, and regulatory pathways. Protein expression profiles showed significant enrichment of dysregulated proteins involved in metabolism, adhesion, cell-ECM interactions, and N-linked glycosylation, supporting the protein glycosylation results. The present case series study provides the first demonstration of a multi-platform mass-spectrometric analysis specifically for Filipino lung cancer patients.

摘要

肺癌是癌症死亡的主要原因,非小细胞肺癌(NSCLC)占肺癌的大多数。因此,找到潜在的生物标志物,如聚糖和糖蛋白,作为针对NSCLC的诊断工具非常重要。在此,对菲律宾肺癌患者(n = 5)肿瘤和瘤周组织的N-糖组、蛋白质组和N-糖基化分布图进行了表征。我们展示了几个不同癌症发展阶段(I-III期)、突变状态以及基于三基因面板(、和)的生物标志物表达的病例研究。尽管每位患者的图谱都是独特的,但出现了与异常糖基化在癌症进展中的作用相关的特定趋势。具体而言,我们观察到肿瘤样本中高甘露糖和唾液酸化岩藻糖基化N-聚糖的相对丰度普遍增加。对每个糖基位点的聚糖分布分析表明,这些唾液酸化岩藻糖基化N-聚糖特异性地附着于参与关键细胞过程的糖蛋白,包括代谢、细胞粘附和调节途径。蛋白质表达谱显示参与代谢、粘附、细胞-细胞外基质相互作用和N-连接糖基化的失调蛋白显著富集,支持了蛋白质糖基化结果。本病例系列研究首次展示了专门针对菲律宾肺癌患者的多平台质谱分析。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b05/10001221/0741263453df/cancers-15-01559-g001.jpg

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