Krishna Sumanth Nallagangula, V Lakshmaiah, C Muninarayana, K V Deepa, K N Shashidhar
{"title":"A proteomic approach of biomarker candidate discovery for alcoholic liver cirrhosis.","authors":"Krishna Sumanth Nallagangula, V Lakshmaiah, C Muninarayana, K V Deepa, K N Shashidhar","doi":"10.1177/1849454418788417","DOIUrl":null,"url":null,"abstract":"<p><p>Alcoholic liver disease (ALD) progresses from steatosis to alcoholic hepatitis to fibrosis and cirrhosis. Liver biopsy is considered as the gold standard method for diagnosis of liver cirrhosis and provides useful information about damaging process which is an invasive procedure with complications. Existing biomarkers in clinical practice have narrow applicability due to lack of specificity and lack of sensitivity. The objective of this article is to identify proteomic biomarker candidates for alcoholic liver cirrhosis by differential expression analysis between alcoholic liver cirrhotic and healthy subjects. Blood samples were collected from 20 subjects (10 alcoholic liver cirrhosis and 10 healthy) from R. L. Jalapa Hospital and Research Centre, Kolar, Karnataka, India. Differential protein analysis was carried out by two-dimensional electrophoresis after albumin depletion, followed by liquid chromatography-mass spectrometry. The image analysis found 46 spots in cirrhotic gel and 69 spots in healthy gel, of which 14 spots were identified with significant altered expression levels. Based on the protein score and clinical significance, among 14 spots, a total of 28 protein biomarker candidates were identified: 13 with increased expression and 15 with decreased expression were categorized in alcoholic liver cirrhosis compared to healthy subjects. Protein biomarker candidates identified by \"-omics\" approach based on differential expression between alcoholic liver cirrhotic subjects and healthy subjects may give better insights for diagnosis of ALD. Prioritization of candidates identified is a prerequisite for validation regimen. Biomarker candidates require verification that demonstrates the differential expression will remain detectable by assay to be used for validation.</p>","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2018-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1849454418788417","citationCount":"3","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Circulating Biomarkers","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1177/1849454418788417","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2018/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 3
Abstract
Alcoholic liver disease (ALD) progresses from steatosis to alcoholic hepatitis to fibrosis and cirrhosis. Liver biopsy is considered as the gold standard method for diagnosis of liver cirrhosis and provides useful information about damaging process which is an invasive procedure with complications. Existing biomarkers in clinical practice have narrow applicability due to lack of specificity and lack of sensitivity. The objective of this article is to identify proteomic biomarker candidates for alcoholic liver cirrhosis by differential expression analysis between alcoholic liver cirrhotic and healthy subjects. Blood samples were collected from 20 subjects (10 alcoholic liver cirrhosis and 10 healthy) from R. L. Jalapa Hospital and Research Centre, Kolar, Karnataka, India. Differential protein analysis was carried out by two-dimensional electrophoresis after albumin depletion, followed by liquid chromatography-mass spectrometry. The image analysis found 46 spots in cirrhotic gel and 69 spots in healthy gel, of which 14 spots were identified with significant altered expression levels. Based on the protein score and clinical significance, among 14 spots, a total of 28 protein biomarker candidates were identified: 13 with increased expression and 15 with decreased expression were categorized in alcoholic liver cirrhosis compared to healthy subjects. Protein biomarker candidates identified by "-omics" approach based on differential expression between alcoholic liver cirrhotic subjects and healthy subjects may give better insights for diagnosis of ALD. Prioritization of candidates identified is a prerequisite for validation regimen. Biomarker candidates require verification that demonstrates the differential expression will remain detectable by assay to be used for validation.
酒精性肝病(ALD)可从脂肪变性发展到酒精性肝炎、纤维化和肝硬化。肝活检被认为是诊断肝硬化的金标准方法,并提供有关损伤过程的有用信息,这是一种有并发症的侵入性手术。临床实践中现有的生物标志物由于缺乏特异性和敏感性,适用性较窄。本文的目的是通过分析酒精性肝硬化患者与健康受试者之间的差异表达来确定酒精性肝硬化的候选蛋白质组学生物标志物。从印度卡纳塔克邦Kolar的R. L. Jalapa医院和研究中心采集了20名受试者(10名酒精性肝硬化和10名健康受试者)的血液样本。差异蛋白分析采用白蛋白去除后双向电泳,然后采用液相色谱-质谱法。图像分析发现肝硬化凝胶中有46个斑点,健康凝胶中有69个斑点,其中14个斑点的表达水平显著改变。根据蛋白评分和临床意义,在14个点中,共鉴定出28个候选蛋白生物标志物:与健康受试者相比,酒精性肝硬化中表达升高的有13个,表达降低的有15个。通过“组学”方法确定的基于酒精性肝硬化受试者和健康受试者之间差异表达的候选蛋白质生物标志物可能为ALD的诊断提供更好的见解。确定候选人的优先级是验证方案的先决条件。生物标记候选物需要验证,以证明差异表达将继续被用于验证的分析检测到。
期刊介绍:
Journal of Circulating Biomarkers is an international, peer-reviewed, open access scientific journal focusing on all aspects of the rapidly growing field of circulating blood-based biomarkers and diagnostics using circulating protein and lipid markers, circulating tumor cells (CTC), circulating cell-free DNA (cfDNA) and extracellular vesicles, including exosomes, microvesicles, microparticles, ectosomes and apoptotic bodies. The journal publishes high-impact articles that deal with all fields related to circulating biomarkers and diagnostics, ranging from basic science to translational and clinical applications. Papers from a wide variety of disciplines are welcome; interdisciplinary studies are especially suitable for this journal. Included within the scope are a broad array of specialties including (but not limited to) cancer, immunology, neurology, metabolic diseases, cardiovascular medicine, regenerative medicine, nosology, physiology, pathology, technological applications in diagnostics, therapeutics, vaccine, drug delivery, regenerative medicine, drug development and clinical trials. The journal also hosts reviews, perspectives and news on specific topics.