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基于二维凝胶电泳和质谱联用并经验证的整合蛋白质组学:口腔黏膜下纤维化生物标志物集的鉴定——一项印度研究

Integrated Proteomics Based on 2D Gel Electrophoresis and Mass Spectrometry with Validations: Identification of a Biomarker Compendium for Oral Submucous Fibrosis-An Indian Study.

作者信息

Venugopal Divyambika Catakapatri, Ravindran Soundharya, Shyamsundar Vidyarani, Sankarapandian Sathasivasubramanian, Krishnamurthy Arvind, Sivagnanam Ananthi, Madhavan Yasasve, Ramshankar Vijayalakshmi

机构信息

Department of Oral Medicine and Radiology, Sri Ramachandra Institute of Higher Education and Research (DU), Porur, Chennai 600116, India.

Department of Preventive Oncology (Research), Cancer Institute (WIA), Adyar, Chennai 600020, India.

出版信息

J Pers Med. 2022 Feb 3;12(2):208. doi: 10.3390/jpm12020208.

Abstract

Oral Submucous Fibrosis (OSMF) is a chronic debilitating disease more frequently found in the South East Asian population. This disease poses a public health priority, as it is grouped under oral potentially malignant disorders, with malignant transformation rates of around 7 to 13%. Hence, early identification of high-risk OSMF patients is of the utmost importance to prevent malignant transformation. Proteomic expression profiling is a promising method for identifying differentially expressed proteins for disease prognosis and risk stratification in OSMF. In this study, overexpressed proteins in OSMF, OSMF transformed into oral squamous cell carcinoma (OSCC) and normal tissues were evaluated by proteomic analysis using two-dimensional electrophoresis (2DE) and mass spectrometry, which revealed 23 upregulated proteins. Validation was done using immunohistochemistry for three secretory proteins, namely 14-3-3ε ( = 130), carbonic anhydrase 1 (CA 1) ( = 125) and heat shock protein 70 (HSP 70) ( = 117), which showed significant overexpression in OSMF, OSCC compared to normal. The present study is the first of its kind in India to the best of our knowledge, assessing the altered expression of proteins in OSMF and OSMF which has undergone malignant transformation, obtaining a better knowledge of the molecular pathways involved in the disease progression. The current study shows that the biomarkers studied can be potentially useful for risk stratification of OSMF to OSCC serving as novel targets for therapeutic intervention. Clinical validation of the targets can further pave way for precision medicine to improve the quality of life in OSMF patients.

摘要

口腔黏膜下纤维化(OSMF)是一种慢性致残性疾病,在东南亚人群中更为常见。这种疾病是口腔潜在恶性疾病之一,恶性转化率约为7%至13%,因此成为公共卫生重点关注对象。所以,早期识别OSMF高危患者对于预防恶性转化至关重要。蛋白质组表达谱分析是一种很有前景的方法,可用于识别OSMF疾病预后和风险分层中差异表达的蛋白质。在本研究中,通过二维电泳(2DE)和质谱联用的蛋白质组学分析,评估了OSMF、已转化为口腔鳞状细胞癌(OSCC)的OSMF以及正常组织中过表达的蛋白质,共发现23种上调蛋白。使用免疫组织化学方法对三种分泌蛋白进行验证,即14-3-3ε(n = 130)、碳酸酐酶1(CA 1)(n = 125)和热休克蛋白70(HSP 70)(n = 117),结果显示与正常组织相比,这些蛋白在OSMF和OSCC中显著过表达。据我们所知,本研究是印度首例此类研究,评估了OSMF及发生恶性转化的OSMF中蛋白质表达的变化,从而更好地了解疾病进展过程中涉及的分子途径。当前研究表明,所研究的生物标志物可能有助于OSMF向OSCC转化的风险分层,可作为治疗干预的新靶点。对这些靶点进行临床验证可为精准医学进一步铺平道路,以提高OSMF患者的生活质量。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1be1/8878868/faecc4b6140a/jpm-12-00208-g001.jpg

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