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采用甜蜜策略鉴定口腔鳞状细胞癌中的潜在糖蛋白生物标志物。

Identification of potential glycoprotein biomarkers in oral squamous cell carcinoma using sweet strategies.

机构信息

Department of Oral & Craniofacial Sciences, Faculty of Dentistry, University of Malaya, 50603, Kuala Lumpur, Malaysia.

Department of Oral & Maxillofacial Clinical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.

出版信息

Glycoconj J. 2021 Feb;38(1):1-11. doi: 10.1007/s10719-021-09973-z. Epub 2021 Feb 6.

Abstract

The prevalence of oral squamous cell carcinoma (OSCC) is high in South and Southeast Asia regions. Most OSCC patients are detected at advanced stages low 5-year survival rates. Aberrant expression of glycosylated proteins was found to be associated with malignant transformation and cancer progression. Hence, identification of cancer-associated glycoproteins could be used as potential biomarkers that are beneficial for diagnosis or clinical management of patients. This study aims to identify the differentially expressed glycoproteins using lectin-based glycoproteomics approaches. Serum samples of 40 patients with OSCC, 10 patients with oral potentially malignant disorder (OPMD), and 10 healthy individuals as control group were subjected to two-dimensional gel electrophoresis (2-DE) coupled with lectin Concanavalin A and Jacalin that specifically bind to N- and O-glycosylated proteins, respectively. Five differentially expressed N- and O-glycoproteins with various potential glycosylation sites were identified, namely N-glycosylated α1-antitrypsin (AAT), α2-HS-glycoprotein (AHSG), apolipoprotein A-I (APOA1), and haptoglobin (HP); as well as O-glycosylated AHSG and clusterin (CLU). Among them, AAT and APOA1 were further validated using enzyme-linked immunosorbent assay (ELISA) (n = 120). It was found that AAT and APOA1 are significantly upregulated in OSCC and these glycoproteins are independent risk factors of OSCC. The clinical utility of AAT and APOA1 as potential biomarkers of OSCC is needed for further evaluation.

摘要

口腔鳞状细胞癌(OSCC)在南亚和东南亚地区的发病率很高。大多数 OSCC 患者在晚期被发现,生存率较低。异常表达的糖基化蛋白与恶性转化和癌症进展有关。因此,鉴定癌相关糖蛋白可以作为潜在的生物标志物,有助于患者的诊断或临床管理。本研究旨在使用基于凝集素的糖蛋白质组学方法鉴定差异表达的糖蛋白。40 例 OSCC 患者、10 例口腔潜在恶性疾病(OPMD)患者和 10 例健康对照者的血清样本进行二维凝胶电泳(2-DE),分别用凝集素刀豆球蛋白 A 和 Jacalin 进行处理,刀豆球蛋白 A 特异性结合 N-糖基化蛋白,Jacalin 特异性结合 O-糖基化蛋白。鉴定出 5 种差异表达的 N-和 O-糖蛋白,具有不同的潜在糖基化位点,分别为 N-糖基化α1-抗胰蛋白酶(AAT)、α2-HS-糖蛋白(AHSG)、载脂蛋白 A-I(APOA1)和触珠蛋白(HP);以及 O-糖基化 AHSG 和簇蛋白(CLU)。其中,AAT 和 APOA1 进一步使用酶联免疫吸附试验(ELISA)(n=120)进行验证。结果发现 AAT 和 APOA1 在 OSCC 中显著上调,这些糖蛋白是 OSCC 的独立危险因素。AAT 和 APOA1 作为 OSCC 潜在生物标志物的临床应用价值需要进一步评估。

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