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A specific gene-expression signature quantifies the degree of hepatic fibrosis in patients with chronic liver disease

摘要AIM: To study a more accurate quantification of hepatic fibrosis which would provide clinically 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 azan stained: 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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作者单位 Department of Molecular and Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan [1] Department of Surgery, Iizuka Hospital,Iizuka, Japan [2] Department of Digestive Surgery, Toranomon Hospital and Okinaka Memorial Institute for Medical Research,Tokyo, Japan [3] Department of Surgery, Oita Red Cross Hospital, Oita, Japan [4] Department of Surgery, Hiroshima Red Cross Hospital and Atomic Bomb Survivors Hospital, Hiroshima, Japan [5] Department of Anatomic pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan [6] Department of Pathology, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan [7] Laboratory for Bioinformatics, Graduate School of Systems Life Sciences, Kyushu University, Fukuoka, Japan [8] Division of Gastroenterology, University of Massachusetts Medical School, Worcester, MA, United States [9]
分类号 R5(内科学)
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发布时间 2007-03-20(万方平台首次上网日期,不代表论文的发表时间)
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