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可溶性血管内皮生长因子受体-2作为慢性肝病和肝细胞癌病情进展的预测因子

Soluble Vascular Endothelial Growth Factor Receptor-2 as a Predictive Factor for Progression of Illness in Chronic Liver Diseases and Hepatocellular Carcinoma.

作者信息

Ratnasari Neneng, Nurdjanah Siti, Sadewa Ahmad Hamim, Hakimi Mohammad, Yano Yoshihiko

机构信息

Internal Medicine Department, Faculty of Medicine Gadjah Mada University/ Dr. Sardjito Hospital, Kesehatan Street No. 1, Sekip, Yogyakarta, Indonesia. 55281.

Biochemistry Department, Faculty of Medicine Gadjah Mada University, Yogyakarta, Indonesia.

出版信息

Kobe J Med Sci. 2015 Dec 18;61(3):E89-96.

Abstract

Angiogenesis is generally induced in the process of necro-inflammation and regeneration in chronic liver diseases (CLD). Whereas VEGF is a major humoral factor in relation to neo-vascularization, the receptor, VEGFR-2, is located in hepatocytes and sinusoid endothelial cells. The aim in this study is to investigate the significance of soluble form of VEGFR-2 (sVEGFR-2) in various CLDs. A cross sectional study was conducted from 2010 to 2013 at Dr. Sardjito Hospital Yogyakarta, Indonesia. 149 patients with chronic hepatitis (CH), liver cirrhosis (LC) or hepatocellular carcinoma (HCC) were enrolled in this study. sVEGFR-2 serum was examined using Quantikine®HS kit human immunoassay. Data were analyses by STATA (P value <0.05). The median of sVEGFR-2 was decreased according to the disease progression (LC: 7014.95 pg/mL; CH: 8805.15 pg/mL; healthy subject: 9785.2 pg/mL). However, sVEGFR-2 in HCC (8043.73 pg/mL) was significantly higher than that in LC (P= 0.0059). Based on AUROC analyses, the clinical cut-off point of sVEGFR-2 with >80% sensitivity was used (CH-LC ≤7236.7, LC-HCC ≥7215). The odds ratio (OR) LC to HCC was 5.87 and CH to LC was 4.63. The significant correlations were showed significantly between sVEGFR-2 with MELD and ALT in LC, and with APRI and FIB-4 in CH. In conclusion, the serum sVEGFR-2 could be used as a predictive factor progressing CH to LC, but not HCC.

摘要

血管生成通常在慢性肝病(CLD)的坏死性炎症和再生过程中被诱导。虽然血管内皮生长因子(VEGF)是与新血管形成相关的主要体液因子,但其受体血管内皮生长因子受体-2(VEGFR-2)位于肝细胞和窦状内皮细胞中。本研究的目的是探讨可溶性VEGFR-2(sVEGFR-2)在各种慢性肝病中的意义。2010年至2013年在印度尼西亚日惹萨迪托博士医院进行了一项横断面研究。本研究纳入了149例慢性肝炎(CH)、肝硬化(LC)或肝细胞癌(HCC)患者。使用Quantikine®HS试剂盒人类免疫分析法检测血清sVEGFR-2。数据采用STATA进行分析(P值<0.05)。sVEGFR-2的中位数随疾病进展而降低(LC:7014.95 pg/mL;CH:8805.15 pg/mL;健康受试者:9785.2 pg/mL)。然而,HCC患者的sVEGFR-2(8043.73 pg/mL)显著高于LC患者(P = 0.0059)。基于曲线下面积(AUROC)分析,使用了灵敏度>80%的sVEGFR-2临床截断点(CH-LC≤7236.7,LC-HCC≥7215)。LC与HCC的比值比(OR)为5.87,CH与LC的比值比为4.63。在LC中,sVEGFR-2与终末期肝病模型(MELD)和丙氨酸转氨酶(ALT)之间,以及在CH中与天冬氨酸氨基转移酶与血小板比值指数(APRI)和FIB-4之间均显示出显著相关性。总之,血清sVEGFR-2可作为CH进展为LC的预测因子,但不能作为CH进展为HCC的预测因子。

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