Investigating the potential of circulating microRNAs as non-invasive biomarkers in cirrhosis and hepatocellular carcinoma

Abstract

Identification of 5 miRNA candidates (miRNA-10a-5p, miRNA-10b-5p, miRNA101-3p, miRNA 22-3p and miRNA-27b-3p) in the serum of 136 patients with cirrhosis that are differentially expressed according to disease severity in compensated cirrhosis (n=30), cirrhosis with varices (n=30), cirrhosis with ascites ± varices (n=60), and cirrhosis with variceal bleeding (n=16). MiRNA panels were assembled to distinguish patients with specific complications with the following diagnostic performance: • Varices panel (miRNA-10b-5p + miRNA-101-3p) with an AUC of 0.78 (95% CI 0.66-0.90, p<0.001) • Ascites panel (miRNA-10a-5p + miRNA-146a-5p) with an AUC of 0.83 (95% CI 0.75-0.92, p<0.001) • Variceal bleeding panel (miRNA-10a-5p) with an AUC of 0.80 (95% CI 0.65-0.95, p<0.001) • Decompensation panel, grouping ascites and variceal bleeding patients (miRNA-10a-5p, miRNA-146a-5p + miRNA-423-3p) with an AUC of 0.78 (95% CI 0.70-0.86, p<0.001). Combining platelet count < 150 (x10 9 /L) 2 with the miRNA panels improved the performance of the Varices panel and the Ascites panel (with AUCs of 0.84 and AUC of 0.87, respectively). This thesis has identified several differentially-expressed miRNA candidates across a clinically relevant spectrum of CLD and assembled promising panels of miRNAs that warrant further investigation for their diagnostic potential. Preliminary efforts to explore the possible functional roles of 2 candidates in HCC were unrewarding but further studies can build on these findings by optimising experimental conditions, validating identified miRNA candidates, and testing the prognostic potential of validated miRNAs as clinically-useful non-invasive biomarkers.

Multifaceted roles of extracellular RNAs in different diseases

“…An extensive investigation of proteomics through the serum of liver cancer patients, liver cirrhosis patients and control patients verified a hypothesis differentiating liver cancer and liver cirrhosis [ 67 ]. miRNA-451a was shown to be differentially expressed in the serum of 25 liver cirrhosis patients with early-stage liver cancer in comparison with 74 cirrhotic patients without liver cancer [ 68 ]. Nonalcoholic steatohepatitis (NASH) can lead to liver fibrosis; for example, miR-122 is an early biomarker for liver injury due to NASH.…”

Ras-related associated with diabetes genes for biomarker-based therapeutics in cancer

“…Lower RRAD regulation has, thus, become an independent prognostic marker for the endurance of HCC patients. 6 , 21 Moreover, RRAD restrains hepatoma cell oxygen-consuming glycolysis by contrarily controlling the activity of GLUT1 and hexokinase II. What is more, RRAD restraint significantly expands hepatoma cell intrusion and metastasis.…”