Transcriptomic Analysis Reveals the Messenger RNAs Responsible for the Progression of Alcoholic Cirrhosis.
Transcriptomic Analysis Reveals the Messenger RNAs Responsible for the Progression of Alcoholic Cirrhosis.
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DOI：
10.1002/hep4.1903
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发表时间：
2022-06
影响因子：
5.1
通讯作者：
中科院分区：
文献类型：
--
作者：
酒精相关性肝病是慢性肝病的主要病因。我们假设特定编码基因的表达对酒精性肝硬化（AC）从代偿期到失代偿期的进展至关重要。在发现阶段，我们对16份外周血RNA样本（4例健康对照（HCs）和12例AC患者）进行了RNA测序分析。在另外一组17例HCs和48例AC患者（17例Child - Pugh A级、16例Child - Pugh B级和15例Child - Pugh C级）中，通过定量聚合酶链反应验证了来自发现队列的差异表达基因（DEGs）。我们观察到，随着疾病严重程度的加重，差异表达信使RNA（mRNAs）的数量更加显著。对Child - Pugh A级患者的差异表达基因进行的通路分析显示，涉及先天免疫反应的基因；Child - Pugh B级患者的相关基因属于与氧化和可变剪接有关的基因；Child - Pugh C级患者的相关基因与甲基化、乙酰化和可变剪接有关。我们发现，与存活者相比，在随访期间死亡者的外周血中血红素加氧酶1（HMOX1）和核糖核蛋白PTB结合1（RAVER1）的表达存在显著差异。结论：通过转录组学方法确定了可能与AC患者疾病进展有关的独特mRNAs。需要进一步的研究来证实我们的结果，并且应该进一步探索这些基因在AC发病机制和进展中的影响的综合机制研究。
Alcohol‐associated liver disease is the leading cause of chronic liver disease. We hypothesized that the expression of specific coding genes is critical for the progression of alcoholic cirrhosis (AC) from compensated to decompensated states. For the discovery phase, we performed RNA sequencing analysis of 16 peripheral blood RNA samples, 4 healthy controls (HCs) and 12 patients with AC. The DEGs from the discovery cohort were validated by quantitative polymerase chain reaction in a separate cohort of 17 HCs and 48 patients with AC (17 Child‐Pugh A, 16 Child‐Pugh B, and 15 Child‐Pugh C). We observed that the numbers of differentially expressed messenger RNAs (mRNAs) were more pronounced with worsening disease severity. Pathway analysis for differentially expressed genes for patients with Child‐Pugh A demonstrated genes involved innate immune responses; those in Child‐Pugh B belonged to genes related to oxidation and alternative splicing; those in Child‐Pugh C related to methylation, acetylation, and alternative splicing. We found significant differences in the expression of heme oxygenase 1 (HMOX1) and ribonucleoprotein, PTB binding 1 (RAVER1) in peripheral blood of those who died during the follow‐up when compared to those who survived. Conclusion: Unique mRNAs that may implicate disease progression in patients with AC were identified by using a transcriptomic approach. Future studies to confirm our results are needed, and comprehensive mechanistic studies on the implications of these genes in AC pathogenesis and progression should be further explored.
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影响因子：
5.5
作者：
Groebner JL;Tuma PL
通讯作者：
Tuma PL
影响因子：
65.1
作者：
Gilmore, William;Chikritzhs, Tanya;Gilmore, Ian
通讯作者：
Gilmore, Ian
影响因子：
13.5
作者：
Mandrekar, Pranoti;Bataller, Ramon;Tsukamoto, Hidekazu;Gao, Bin
通讯作者：
Gao, Bin
DOI：
10.3390/v4040581
发表时间：
2012-04
期刊：
Viruses
影响因子：
--
作者：
Papic N;Maxwell CI;Delker DA;Liu S;Heale BS;Hagedorn CH
通讯作者：
Hagedorn CH
影响因子：
29.4
作者：
Liangpunsakul S;Haber P;McCaughan GW
通讯作者：
McCaughan GW