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通过比较蛋白质组学方法鉴定 GIMAP7 和 Rabl3 作为口腔鳞状细胞癌的潜在生物标志物。

Identification of GIMAP7 and Rabl3 as Putative Biomarkers for Oral Squamous Cell Carcinoma Through Comparative Proteomic Approach.

机构信息

National Center for Proteomics, University of Karachi, 75270, Karachi, Pakistan.

出版信息

Pathol Oncol Res. 2020 Jul;26(3):1817-1822. doi: 10.1007/s12253-019-00775-1. Epub 2019 Nov 20.

DOI:10.1007/s12253-019-00775-1
PMID:31748878
Abstract

Oral squamous cell carcinoma (OSCC) accounts for more than 90% of all oral cancers and has been listed as sixth most common human cancer. Due to late diagnosis and insufficient therapeutic response among patients, the survival rate remains very low accentuating the importance of early diagnostic markers. The study aimed to identify differentially expressed proteins in search for putative serum biomarkers and drug targets. Serum samples (n = 45) were depleted and resolved on two dimensional gel electrophoresis. Among differentially expressed proteins, two were identified using MALDI-TOF mass spectrometry. Gene expression levels of identified proteins were quantified in malignant and normal tissue using RT-qPCR. To validate serum Rabl3 expression, sandwich ELISA was performed. Proteomics analysis revealed two proteins which were found to be associated with oral cancer. The expression of GIMAP7 was found to be down regulated in serum of patients suffering from oral cancer while the expression of Rabl3 was found to be up-regulated. Gene expression analysis in malignant tissue and adjacent normal tissue revealed the same pattern. Quantitative ELISA was used to validate expression of Rabl3 in serum from oral cancer patients and healthy subjects which demonstrated significant up-regulation in cancer patients. Findings in current study demonstrate differential expression of novel putative biomarkers GIMAP7 and Rabl3 in oral cancer which suggests their potential role in oral cancer pathology and can be considered as predictive biomarkers.

摘要

口腔鳞状细胞癌(OSCC)占所有口腔癌的 90%以上,已被列为第六大常见人类癌症。由于患者诊断较晚和治疗反应不足,生存率仍然很低,这凸显了早期诊断标志物的重要性。本研究旨在鉴定差异表达蛋白,以寻找潜在的血清生物标志物和药物靶点。采集 45 例血清样本进行脱沉和二维凝胶电泳分析。在差异表达的蛋白中,使用 MALDI-TOF 质谱鉴定了两种蛋白。采用 RT-qPCR 定量检测恶性和正常组织中鉴定蛋白的基因表达水平。为了验证血清 RabL3 的表达,进行了夹心 ELISA 实验。蛋白质组学分析显示两种蛋白与口腔癌相关。GIMAP7 在口腔癌患者血清中的表达下调,而 RabL3 的表达上调。对恶性组织和相邻正常组织的基因表达分析显示出相同的模式。定量 ELISA 用于验证口腔癌患者和健康受试者血清中 RabL3 的表达,结果表明癌症患者的表达显著上调。本研究发现口腔癌中新型潜在生物标志物 GIMAP7 和 RabL3 的差异表达,提示其在口腔癌发病机制中的潜在作用,可作为预测性生物标志物。

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