Open AccessTranscriptomic Analysis Reveals the Messenger RNAs Responsible for the Progression of Alcoholic Cirrhosis
Author(s) -
Yang Zhihong,
Han Sen,
Zhang Ting,
Kusumanchi Praveen,
Huda Nazmul,
Tyler Kelsey,
Chandler Kristina,
Skill Nicholas J.,
Tu Wanzhu,
Shan Mu,
Jiang Yanchao,
Maiers Jessica L.,
Perez Kristina,
Ma Jing,
Liangpunsakul Suthat
Publication year - 2022
Publication title -
hepatology communications
Language(s) - English
Resource type - Journals
ISSN - 2471-254X
DOI - 10.1002/hep4.1903
Subject(s) - transcriptome , biology , alcoholic liver disease , gene , rna splicing , alternative splicing , gene expression , messenger rna , cirrhosis , rna , cancer research , medicine , genetics
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.