MicroRNA profiles in serum samples from Acute-On-Chronic Liver Failure patients and miR-25-3p as a potential biomarker for survival prediction

Abstract

Acute-on-chronic liver failure (ACLF) is a condition characterized by acute decompensation of cirrhosis, associated with organ failure(s), and high short-term mortality. The microRNAs or miRNAs are small non-coding RNA molecules, stable in circulating samples such as biological fluids, and the difference in expression levels may indicate the presence, absence and/or stage of the disease. We analyzed here the miRNA profiling to identify potential diagnostic or prognostic biomarkers for ACLF. The major miRNAs discovered were validated in a cohort of patients with acute decompensation of cirrhosis grouped in no ACLF or ACLF according to EASL-CLIF definition. Relationship between serum miRNAs and variables associated with liver-damage and survival outcomes were verified to identify possible prognostic markers. Our results showed twenty altered miRNAs between no ACLF and ACLF patients, and twentyseven in patients who died in 30 days compared with who survived. In validation phase, miR-223-3p and miR-25-3p were significantly altered in ACLF patients and in those who died in 30 days. miR-223-3p and miR-25-3p expression were associated with the lowest survival in 30 days. The decrease in miR-223-3p and miR-25-3p expression was associated with the presence of ACLF and poor prognosis. Of these, miR-25-3p was independently related to ACLF and 30-day mortality. The natural history of cirrhosis is usually characterized by a long-standing compensated phase followed by a transition to the decompensated disease, identified by the occurrence of specific complications of cirrhosis, such as ascites, variceal bleeding, and hepatic encephalopathy 1. Patients with both compensated or decompensated cirrhosis are at risk of progression to acute-on-chronic liver failure (ACLF), a condition characterized by an acute deterioration of the liver function and characterized by progression to extrahepatic organ failure and high short-term mortality 2,3. Although a precise definition is still lacking, the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) Consortium definition is one of the most validated criteria for ACLF in patients with cirrhosis and it is based on a modified version of SOFA score called CLIF-SOFA 2,4. According to a recently published study 5 , mortality rates in ACLF patients are 25.5% and 40% in 28 and 90 days of admission, respectively. Therefore, searching for new biomarkers associated with the presence of ACLF and prognosis of patients with acute decompensation of cirrhosis may improve clinical decision and help to implement risk-adapted treatment strategies. In recent years, miRNAs have been studied as promising biomarkers for the diagnosis and prognostic in many clinical scenarios 6-8 , including liver diseases 9. The miRNAs are a group of small non-coding RNAs, with approximately 22 nucleotides, which post-transcriptionally regulate gene expression

MiR-25-3p targets PTEN to regulate the migration, invasion, and apoptosis of esophageal cancer cells via the PI3K/AKT pathway

“…Recently, the abnormal expression level of miR-25-3p has been discovered in different diseases gradually. For instance, miR-25-3p was found to be up-regulated in triple-negative breast cancer, osteosarcoma, and gastric cancer [ 12–14 ]; while it was found to be down-regulated in acute-on-chronic liver failure and tongue squamous cell carcinoma [ 15 , 16 ]. In addition, miR-25-3p was proved to be a biomarker for the diagnosis and treatment of many cancers and able to regulate the biological functions of various cells [ 13 , 15 ].…”

“…For instance, miR-25-3p was found to be up-regulated in triple-negative breast cancer, osteosarcoma, and gastric cancer [ 12–14 ]; while it was found to be down-regulated in acute-on-chronic liver failure and tongue squamous cell carcinoma [ 15 , 16 ]. In addition, miR-25-3p was proved to be a biomarker for the diagnosis and treatment of many cancers and able to regulate the biological functions of various cells [ 13 , 15 ]. Besides, miR-25-3p could enhance the proliferation and migration of glioma cells, impair tumorigenesis of gastric cancer and regulate the migration of gastric cancer cells, and promote the pre-metastatic niche formation of colorectal cancer [ 14 , 17 , 18 ].…”

Acute and post-acute phase of COVID-19: Analyzing expression patterns of miRNA-29a-3p, 146a-3p, 155-5p, and let-7b-3p in PBMC

“…In the last decade, more and more evidence has suggested that microRNAs (miRNAs) are promising biomarkers due to their high sensitivity and specificity for the diagnosis of various diseases such as viral infections and cancers [14] , [15] , [16] . In addition, the expression pattern of cellular miRNAs, during the acute phase of the disease, is different from the post-acute phase of the disease [17] , [18] . So, it has the ability to be considered as a prognosis biomarker.…”

Extracellular Vesicles: New Endogenous Shuttles for miRNAs in Cancer Diagnosis and Therapy?

“…Tumor-related alterations in microRNA expression and function can reflect molecular processes of tumor onset and progression qualifying microRNAs as potential diagnostic and prognostic biomarkers. Current investigations show that miRNAs are detectable in different tissue types and a wide range of biological fluids, either free or trapped in circulating EVs [47,48].…”