LncRNA AK054921 and AK128652 are potential serum biomarkers and predictors of patient survival with alcoholic cirrhosis.

LncRNA AK054921 and AK128652 are potential serum biomarkers and predictors of patient survival with alcoholic cirrhosis.
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DOI:
10.1002/hep4.1061
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发表时间:
2017-08
影响因子:
5.1
通讯作者:
Wang L
Wang L
中科院分区:
医学2区
文献类型:
--
作者:
Yang Z;Ross RA;Zhao S;Tu W;Liangpunsakul S;Wang L

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酒精性肝病(ALD)是慢性肝脏疾病的主要原因之一。最近的研究已经证明了长链非编码RNA(lncRNA)在几种疾病过程的发病机制中的作用。然而,lncRNA在ALD患者中的作用仍未探索。在健康对照(HC; n = 4)、无肝病的过量饮酒者(艾德)(n = 4)和具有不同严重程度的酒精性肝硬化(AC)的那些(n = 12)的充分表征的队列中进行来自外周血RNA的人lncRNA的全局分析。在HC(n = 17)、艾德(n = 19)、AC(n = 48)和具有ALD的人肝组织(n = 19)的单独群组中验证独特lncRNA特征的表达。与HC相比,对不同严重程度的AC受试者的血浆lncRNA进行了详细分析,确定了244种常见的上调lncRNA和181种常见的下调lncRNA。我们进一步验证了与HC相比,艾德和AC中上调和下调差异最大的前20种lncRNA,并确定了有或无AC的人肝组织中选定lncRNA的表达。在这些lncRNA中,AK 128652和AK 054921是正常人血浆和肝脏中表达最丰富的两种lncRNA,并且它们的水平在AC中显著升高。在48例AC受试者中确定了AK 128652和AK 054921的预后意义,这些受试者前瞻性随访了520天。AK 128652和AK 054921的表达与AC患者的生存率呈负相关。结论:lncRNA AK 054921和AK 128652是预测过度饮酒个体向ALD进展的潜在生物标志物,并且是AC患者生存的预测因子。(Hepatology Communications 2017;1:513-523)
Alcoholic liver disease (ALD) is one of the leading causes of chronic liver disease. Recent studies have demonstrated the roles of long noncoding RNAs (lncRNAs) in the pathogenesis of several disease processes. However, the roles of lncRNAs in patients with ALD remain unexplored. Global profiling for human lncRNAs from peripheral blood RNA was performed in a well‐characterized cohort of healthy controls (HC; n = 4), excessive drinkers (ED) without liver disease (n = 4), and those with alcoholic cirrhosis (AC) with different severities (n = 12). The expression of unique lncRNA signatures were validated in a separate cohort of HC (n = 17), ED (n = 19), AC (n = 48), and human liver tissues with ALD (n = 19). A detailed analysis of plasma lncRNAs in AC subjects with different severities compared with HC identified 244 commonly up‐regulated lncRNAs and 181 commonly down‐regulated lncRNAs. We further validated top 20 most differentially up‐ and down‐regulated lncRNAs in ED and AC compared with HC and also determined the expression of selected lncRNAs in human liver tissues with or without AC. Among those lncRNAs, AK128652 and AK054921 were two of the most abundantly expressed lncRNAs in normal human plasma and liver, and their levels were significantly elevated in AC. The prognostic significance of AK128652 and AK054921 was determined in 48 subjects with AC who were followed prospectively for 520 days. The expression of AK128652 and AK054921 was inversely associated with survival in patients with AC. Conclusion: lncRNAs AK054921 and AK128652 are potential biomarkers to predict the progression to ALD in individuals with excessive alcohol consumption and are predictors of survival in patients with AC. (Hepatology Communications 2017;1:513–523)
DOI: 10.1002/hep.29209
发表时间: 2017-10
期刊: Hepatology (Baltimore, Md.)
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发表时间: 1965-01-01
影响因子: 15.9
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发表时间: 2016-07
期刊: Diabetes
影响因子: 7.7
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通讯作者: Schaffer JE
DOI: 10.1111/acer.12693
发表时间: 2015-05
期刊: Alcoholism, clinical and experimental research
影响因子: --
作者:
Whitfield JB;Rahman K;Haber PS;Day CP;Masson S;Daly AK;Cordell HJ;Mueller S;Seitz HK;Liangpunsakul S;Westerhold C;Liang T;Lumeng L;Foroud T;Nalpas B;Mathurin P;Stickel F;Soyka M;Botwin GJ;Morgan TR;Seth D;GenomALC Consortium
通讯作者: GenomALC Consortium