Aberrant Concentrations of Liver-Derived Plasma Albumin mRNA in Liver Pathologies
Aberrant Concentrations of Liver-Derived Plasma Albumin mRNA in Liver Pathologies
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DOI：
10.1373/clinchem.2009.133355
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发表时间：
2010-01-01
影响因子：
9.3
通讯作者：
Chiu, Rossa W. K.
中科院分区：
文献类型：
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作者：
Chan, Rebecca W. Y.;Wong, John;Chiu, Rossa W. K.
背景：我们假设肝脏来源的 mRNA，例如 ALB（白蛋白）mRNA，会随着肝细胞死亡而释放到人血浆中。方法：我们通过 RNA 单核苷酸多态性分析，对肝脏和骨髓移植受者的血浆和全血样本中的 ALB mRNA 分子进行基因分型。将血浆和全血 ALB mRNA 基因型与受者和供者的 DNA 基因型进行比较。采用逆转录定量实时 PCR 测定法测量 107 名患者（肝细胞癌 (HCC)、肝硬化或慢性乙型肝炎 (CHB)）和 207 名健康对照者的血浆 ALB mRNA 浓度。 结果：RNA 基因型数据显示血浆中的 ALB mRNA 源自肝脏，而肝脏以外的组织区室也对全血中检测到的 ALB mRNA 产生影响。与对照组相比，在 HCC、肝硬化和活动性 CHB 中观察到血浆 ALB mRNA 浓度显着增加。通过 ROC 曲线分析确定的血浆 ALB mRNA 的截止值为 835 拷贝/mL，显示肝脏病理检测的诊断灵敏度为 85.5%，诊断特异性为 92.8%。只有 21.5% 的肝脏病变患者的丙氨酸转氨酶 (ALT) 活性升高，而 73.8% 的患者血浆 ALB mRNA 浓度升高。只有48.6%的HCC患者血清甲胎蛋白浓度升高，而91.4%的HCC患者血浆ALB mRNA浓度升高。结论：ALB mRNA在血浆中具有肝脏特异性，但在全血中则不然。血浆 ALB mRNA 在某些肝脏病变中增加，可能比甲胎蛋白和 ALT 更具诊断敏感性。 (C) 2009 美国临床化学协会
BACKGROUND: We hypothesized that liver-derived mRNA, such as ALB (albumin) mRNA, would be released into human plasma with liver cell death.METHODS: We genotyped ALB mRNA molecules in samples of plasma and whole blood from liver and bone marrow transplant recipients by RNA single-nucleotide polymorphism analysis. Plasma and whole blood ALB mRNA genotypes were compared with the DNA genotypes of the recipients and donors. A reverse-transcription quantitative real-time PCR assay was used to measure plasma ALB mRNA concentrations in 107 patients [hepatocellular carcinoma (HCC), cirrhosis, or chronic hepatitis B (CHB)] and 207 healthy controls.RESULTS: The RNA genotype data revealed ALB mRNA in plasma to be liver derived, whereas tissue compartments other than the liver also contributed to the ALB mRNA detected in whole blood. Statistically significant increases in plasma ALB mRNA concentrations were observed for HCC, cirrhosis, and active CHB, compared with controls. A cutoff of 835 copies/mL of plasma ALB mRNA identified by ROC curve analysis showed 85.5% diagnostic sensitivity and 92.8% diagnostic specificity for the detection of liver pathologies. Only 21.5% of patients with liver pathologies had increased alanine aminotransferase (ALT) activities, whereas 73.8% had increased plasma ALB mRNA concentrations. Only 48.6% of the HCC patients had increased serum alpha-fetoprotein concentrations, whereas 91.4% had increased plasma ALB mRNA concentrations.CONCLUSIONS: ALB mRNA is liver specific in plasma, but not in whole blood. Plasma ALB mRNA is increased in some liver pathologies and may be more diagnostically sensitive than alpha-fetoprotein and ALT. (C) 2009 American Association for Clinical Chemistry