Circular RNAs 0064286 and 0000475: Potential Diagnostic Biomarkers in Hepatocellular Carcinoma.

Fathia Zaky El Sharkawi,M Samy Awad,Waleed Elagawy,H.A Al Sawaf,Heba Taha

doi:10.31557/apjcp.2021.22.9.3039

Abstract

Objective:Hepatocellular carcinoma (HCC) is considered the highest recorded malignancy in Egypt. The shortage of appropriate biomarkers for early detection often results in the late diagnosis of the HCC. Circular RNAs (CircRNAs) are presented as long stranded non-coding RNA that combine covalently to make a sealed circular form which make them very stable. CircRNAs are known to have interpretative role in cancer development and metastasis. Aim:To examine the dysregulation of two new CircRNAs obtained from Circbase database (hsa_circ_0064286 and hsa_circ_0000475) in the serum of HCC patients as predictable diagnostic biomarkers of HCC and their correlation with some liver biochemical parameters. Methods:Sixty clinically diagnosed HCC Egyptian patients and 25 healthy volunteers were enrolled in the study. Expression levels of the selected CircRNAs was evaluated in subjects’ serum. Moreover, correlation with liver biochemical parameters, sensitivity, and specificity of studied CircRNAs were estimated. Results:Both circular RNAs were significantly down regulated in HCC patients, which was negatively correlated with ALP, ALT, AST, AFP, and bilirubin levels. Circ_0064286 showed more sensitivity and specificity (88.3% and 96%, respectively). Conclusion:As far as we know, this is the first study that shed light on the expression levels of both circRNAs in Egyptian HCC patients. They may serve as potential biomarkers for HCC diagnosis. Moreover, those circRNAs draw attention as therapeutic targets for HCC through targeting their sponge miRNAs.

Highlights

Hepatocellular carcinoma (HCC) is characterized by progressive genetic mutations resulting in altering the phenotype of the hepatocytes (Bruix et al, 2014)
Venous blood samples were drawn from each subject for serum separation and kept at -80°C till analysis; serum was separated for determination of hsa_circ_0064286, hsa_circ_0000475 and liver biochemical parameters [AFP, alkaline phosphatases (ALP), alanine transaminases (ALT), bilirubin, aspartate transaminase (AST), and albumin]
Some CircRNAs have been reported in HCC either by increasing or decreasing in their expression levels, the expression levels of both hsa_circ_0005986 (Fu et al, 2017) and circMTO1 (Han et al, 2017) are

Summary

Introduction

Hepatocellular carcinoma (HCC) is characterized by progressive genetic mutations resulting in altering the phenotype of the hepatocytes (Bruix et al, 2014). HCC ranks sixth in cancer prevalence, while in terms of mortality rate, it is the fourth worldwide (Bray et al, 2018). Imaging techniques shows a vital role in HCC diagnosis, multiphase computerized tomography (CT) or screening by magnetic resonance imagining (MRI) is acclaimed for initial diagnostic testing (Marrero et al, 2018). Blood biomarkers would be extremely important for early diagnosis, prognosis and response to therapy in HCC patients. The most widely used blood biomarker was alpha-fetoprotein (AFP), AFP has several limitations as lower sensitivity and weak specificity, making its use not satisfactory enough in the diagnosis of HCC (Chen et al, 2003). There is an imperative necessity to develop new diagnostic biomarkers with higher sensitivity and specificity

Methods

Results

Conclusion