A specific gene-expression signature quantifies the degree of hepatic fibrosis in patients with chronic liver disease
A specific gene-expression signature quantifies the degree of hepatic fibrosis in patients with chronic liver disease作者机构：Department of Molecular and Surgical Oncology Medical Institute of Bioregulation Kyushu University Beppu Japan Department of Surgery Iizuka Hospital Iizuka Japan Department of Digestive Surgery Toranomon Hospital and Okinaka Memorial Institute for Medical Research Tokyo Japan Department of Surgery Oita Red Cross Hos-pital Oita Japan Department of Surgery Hiroshima Red Cross Hospital and Atomic Bomb Survivors Hospital Hiroshima Japan Department of Anatomic pathology Graduate School of Medical Sciences Kyushu University Fukuoka Japan Department of Pathology Medical Institute of Bioregulation Kyushu University Beppu Japan Laboratory for Bioinformatics Graduate School of Systems Life Sciences Kyushu University Fukuoka Japan Division of Gastroenterology University of Massachusetts Medical School Worcester MA United States
出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)
年 卷 期：2007年第13卷第3期
页 面：383-390页
核心收录：
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
基 金：Supported partly by Grants-in-Aid for Scientific Research (S) (17109013) and for Scientific Research (C) (17591411 and 15591411) a Health and Labor Sciences Research Grant on Hepatitis and BSE (14230801) the Uehara Memorial Foundation, Yasuda Medical Research Foundation, Japanese Foundation for Multidisciplinary Treatment of Cancer, and Princes Takamatsu Cancer research Fund
主 题：Uver fibrosis Hepatitis virus DNA microarray Supervised learning analysis Scoring system
摘 要：AIM： To study a more accurate quantification of hepatic fibrosis which would provide dinically useful information for monitoring the progression of chronic liver disease. METHODS： Using a cDNA microarray containing over 22000 clones, we analyzed the gene-expression profiles of non-cancerous liver in 74 patients who underwent hepatic resection. We calculated the ratio of azanstained： total area, and determined the morphologic fibrosis index （MFI）, as a mean of 9 section-images. We used the MFI as a reference standard to evaluate our method for assessing liver fibrosis. RESULTS： We identified 39 genes that collectively showed a good correlation （r 〉 0.50） between geneexpression and the severity of liver fibrosis. Many of the identified genes were involved in immune responses and cell signaling. To quantify the extent of liver fibrosis, we developed a new genetic fibrosis index （GFI） based on gene-expression profiling of 4 clones using a linear support vector regression analysis. This technique, based on a supervised learning analysis, correctly quantified the various degrees of fibrosis in both 74 training samples （r = 0.76, 2.2% vs 2.8%, P 〈 0.0001） and 12 independent additional test samples （r = 0.75, 9.8% vs 8.6%, P 〈 0.005）. It was far better in assessing liver fibrosis than blood markers such as prothrombin time （r = -0.53）, type IV collagen 7s （r = 0.48）, hyaluronic acid （r = 0.41）, and aspartate aminotransferase to platelets ratio index （APRI） （r = 0.38）. CONCLUSION： Our cDNA microarray-based strategy may help clinicians to precisely and objectively monitor the severity of liver fibrosis.
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