Study of MicroRNA 203 and Its Target Genes (Survivin, Cyclin-D) in Circulating Liver Cancer Stem Cells in Patients with Chronic Hepatitis C with and without HCC
Authors: Foda Enas Mahmoud , Elshafie Ahmed Ibrahim Mohamed , Ali Ali Abdel Rahim , Anwar Christina Alphonse , Mohamed Omar Mohamed 
Published: August 2023

Abstract

Background
Hepatitis C virus (HCV) infection is a significant cause of morbidity and mortality, infecting more than 180 million people worldwide. Chronic viral infection is one of the most common causes of hepatic fibrosis, distortion of the hepatic architecture, and ultimate progression to cirrhosis of the liver. HCV infection inflames the liver which, if unmanaged, will inevitably result in fibrosis and then progress to cirrhosis which has many co-morbid complications such as hepatocellular carcinoma (HCC). HCC is an aggressive tumor usually involving late stage liver cancers when diagnosed. Although significant progress regarding the treatment options for HCC has been made in recent years, poor prognosis remains a problem because of late diagnosis and drug resistance, making recurrence almost inevitable.

Objective
to compare level of miRNA 203 and its target genes (Survivin, Cyclin-D) in circulating liver cancer stem cells in patients with chronic hepatitis C with and without H.C.C.

Patients and Methods
This study was conducted in co-operation between Gastroenterology and Hepatology Department, Ain-Shams University and the Gastroenterology and Hepatology Department, Theodor Bilharz Research Institute “between” April 2021 to October 2021.It included total participants of 80 divided to 4 GrousGroup A (HCV group): twenty patients infected with HCV without liver cirrhosis.Group B (LC group): twenty patients infected with HCV with liver cirrhosis.Group C (HCC group): twenty patients infected with HCV with HCC.Control group: twenty normal populations.

Results
our study demonstrated that the level of miRNA 203 showed statistically significant difference between all study groups with lowest level was found in HCC group and highest level was in control group with statistically significant decrease in HCC group than LC and other groups. The study also demonstrated that circulating level of Survivn shows significant increase in HCC group than other study groups. With no significant changes in its level between non HCC groups (Control, HCV and LC groups).The circulating Cyclin D level showed significant increase in HCC group than other study groups, With statistically significant increase in its level in LC group than control and non-cirrhotic HCV group. The study markers (miRNA 203, Survivn and Cyclin D) showed no significant relation between their levels in HCC patients and AFP level. Also, no significant relation was established between (miRNA 203, Survivn and Cyclin D) and PVT, number of focal lesions, largest diameter of the lesion or BCLC.

Conclusion
miRNA 203 level in circulating CSCs showed significant changes according to the stage of HCV related disease with lowest level is seen in HCC patients.Survivin level in circulating CSCs showed significant increase in HCC patients with no significant difference between other groups, and this indicates that changes in its level is highly specific for malignant transformation.Cyclin D level in circulating CSCs showed significant increase in HCC patiens than other study groups, with increase in its level in LC patients than control and non-cirrhotic HCV patients, and this indicates that the changes in its level start with cirrhosis process. No relation was established between (circulating miRNA 203, Survivn and Cyclin D) and AFP, PVT, number of focal lesions, largest diameter of the lesion or BCLC.