Comparison of circulating, hepatocyte specific messenger RNA and microRNA as biomarkers for chronic hepatitis B and C.
Comparison of circulating, hepatocyte specific messenger RNA and microRNA as biomarkers for chronic hepatitis B and C.
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循环肝细胞特异性信使 RNA 和 microRNA 作为慢性乙型和丙型肝炎生物标志物的比较
DOI：
10.1371/journal.pone.0092112
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Yuan Z
中科院分区：
文献类型：
--
作者：
Zhang X;Zhang Z;Dai F;Shi B;Chen L;Zhang X;Zang G;Zhang J;Chen X;Qian F;Hu Y;Yuan Z
在多种生理和病理条件下，循环microRNAs已被广泛认为是一类新的生物标志物。其他报告显示，器官特异性信使RNA片段也可在血清/血浆中检测到，并可用作肝脏病理和癌症的敏感指标。为了评价这两类 = 作为慢性乙型或丙型肝炎标志物的敏感性和可靠性，我们采集了15 6例慢性乙型或丙型肝炎患者(乙肝病毒活动性n = 1 1例，乙肝病毒携带者n = 19例，丙型肝炎n RNA2 5例)和2 2例健康献血员血浆中白蛋白、Hp(结合珠蛋白)、细胞色素P450(家族2，E亚家族)和载脂蛋白A2(ApoA2)的循环m RNA，并结合microRNA-12 2对其进行定量。我们发现，活动性乙肝患者血浆microRNA-122水平显著升高，而乙肝病毒携带者血浆microRNA-122水平无明显变化。此外，即使丙型肝炎患者的血清丙氨酸氨基转移酶(SALT)中位数是健康献血者的三倍，但他们的microRNA-122并未升高。然而，循环中的mRNAs，尤其是白蛋白mRNAs，在区分活动性乙肝、乙肝病毒携带者或丙型肝炎患者与健康对照组方面显示出更高的敏感性。相关分析和多元线性回归分析表明，循环中的mRNAs和miRNAs与HBs Ag滴度的关系远大于与食盐的关系。乙肝患者血浆中乙肝表面抗原的免疫沉淀导致白蛋白和幽门螺杆菌mRNA的浓缩，这表明肝脏特异的转录本片段可以被包裹到乙肝表面抗原颗粒中。综上所述，我们的结果表明，血浆中肝细胞特异性转录物如白蛋白mRNA在区分乙肝病毒或丙型肝炎所致慢性肝病方面比microRNA-122具有更高的敏感性和特异性。在寻找各种疾病的下一代生物标志物方面，循环中的mRNA片段值得更多的关注。
Circulating microRNAs have been widely recognized as a novel category of biomarker in a variety of physiological and pathological conditions. Other reports revealed that fragments of organ specific messenger RNAs are also detectable in serum/plasma and can be utilized as sensitive indicators of liver pathology and cancer. In order to assess the sensitivity and reliability of these two class of RNAs as marker of hepatitis B or C induced chronic liver disease, we collected plasma samples from 156 chronic hepatitis B or C patients (HBV active n = 112, HBV carrier n = 19, hepatitis C n = 25) and 22 healthy donors and quantified their circulating mRNA for albumin, HP (haptoglobin), CYP2E1 (cytochrome P450, family 2, subfamily E) and ApoA2 (Apolipoprotein A2) in conjunction with microRNA-122, a well established marker for acute and chronic liver injury. We found that plasma microRNA-122 level is significantly elevated in patients with active HBV but not in HBV carriers. Furthermore, microRNA-122 is not elevated in HCV patients even though their median serum alanine aminotransferase (sALT) was three fold of the healthy donors. Nevertheless, circulating mRNAs, especially albumin mRNA, showed much more sensitivity in distinguishing active hepatitis B, hepatitis B carrier or HCV patientsfrom healthy control. Correlation and multiple linear regression analysis suggested that circulating mRNAs and miRNAs are much more related to HBsAg titre than to sALT. Immunoprecipitation of HBsAg in HBV patients’ plasma resulted in enrichment of albumin and HP mRNA suggesting that fragments of liver specific transcripts can be encapsidated into HBsAg particles. Taken together, our results suggest that hepatocyte specific transcripts in plasma like albumin mRNA showed greater sensitivity and specificity in differentiating HBV or HCV induced chronic liver disease than microRNA-122. Circulating mRNA fragments merit more attention in the quest of next generation biomarkers for various maladies.
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影响因子：
3.7
作者：
Cheng HR;Liu CJ;Tseng TC;Su TH;Yang HI;Chen CJ;Kao JH
通讯作者：
Kao JH
影响因子：
9.3
作者：
Chan, Rebecca W. Y.;Wong, John;Chiu, Rossa W. K.
通讯作者：
Chiu, Rossa W. K.
影响因子：
3.7
作者：
Gilad S;Meiri E;Yogev Y;Benjamin S;Lebanony D;Yerushalmi N;Benjamin H;Kushnir M;Cholakh H;Melamed N;Bentwich Z;Hod M;Goren Y;Chajut A
通讯作者：
Chajut A
DOI：
10.1073/pnas.0813371106
发表时间：
2009-03-17
影响因子：
11.1
作者：
Wang, Kai;Zhang, Shile;Galas, David J.
通讯作者：
Galas, David J.
影响因子：
11.5
作者：
Wong, SCC;Lo, SFE;Lo, YMD
通讯作者：
Lo, YMD