Serum Exosomal Long Noncoding RNA Growth Arrest-Specific 5 Predicts 3-Month Mortality in Acute-on-Chronic Hepatitis B Liver Failure

Abstract

Background

Acute-on-chronic hepatitis B liver failure (ACHBLF) is a clinical syndrome with an extremely high mortality. In this study, we aim to evaluate the potential role of serum exosomal long noncoding RNA (lncRNA) growth arrest-specific 5 (GAS5) in ACHBLF and its predictive value for 3-month mortality.

Methods

From December 2017 to June 2022, we enrolled 110 patients with ACHBLF and 42 healthy controls (HCs). Exosomes were isolated from the serum of the participants. Serum exosomal lncRNA GAS5 was detected using quantitative real-time polymerase chain reaction (qRT-PCR). The functional role of lncRNA GAS5 on hepatocyte phenotypes was investigated through loss-of-function and gain-of-function assays. Exosomal labeling and cell uptake assay were used to determine the exosomes-mediated transmission of lncRNA GAS5 in hepatocytes in vitro.

Results

The serum exosomal lncRNA GAS5 was identified to be an independent predictor for 3-month mortality of ACHBLF. It yielded an area under the receiver operating characteristic curve (AUC) of 0.88, which was significantly higher than MELD score (AUC 0.73; P < 0.01). Further study found that lncRNA GAS5 could inhibit hepatocytes proliferation and increase hepatocytes apoptosis. Exosomes-mediated lncRNA GAS5 transfer promoted hepatocytes injury. The knocked down of lncRNA GAS5 weakened H₂O₂-induced hepatocytes injury.

Conclusion

We revealed that serum exosomal lncRNA GAS5 might promote hepatocytes injury and showed high predictive value for 3-month mortality in ACHBLF.

Keywords:

• acute-on-chronic hepatitis B liver failure
• exosomes
• long noncoding RNA
• growth arrest-specific 5
• prognosis

Data Sharing Statement

The data underlying this article will be shared on reasonable request to the corresponding author.

Ethics Approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee at Qilu Hospital of Shandong University.

Consent to Participate

Informed consent was obtained from all individual participants included in the study.

Consent to Publish

The authors affirm that human research participants provided informed consent for publication of the article.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare no competing interests in this work.

Additional information

Funding

This work was supported by the National Key Research and Development Program of China (2021YFC2301801), National Natural Science Foundation of China (82272313), Natural Science Foundation of Shandong Province (ZR2022MH006, ZR2020QH287, ZR2016HQ42), Jinan Science and Technology Development Plan (201704094).