Circulating Cancer Associated Fibroblast and Cancer Stem Cell Markers as Diagnostic and Prognostic Tools of Hepatitis C Induced Hepatocellular Carcinoma

BackgroundSeveral studies were carried out on the crosstalk between cancer-associated fibroblasts (CAFs) and liver cancer stem cells (LCSCs) and their role in tumorigenesis and their metastasis of many malignancies, including hepatocellular carcinoma (HCC). Identification of cancer stem cells (CSCs) and CAFs in these studies has typically been carried out based on their markers' expression in hepatic tumor tissues.Objective To detect CAFs and CSCs markers in peripheral blood, which can be used as non-invasive diagnostic and prognostic tools for HCV induced fibrosis and carcinogenesis in Egyptian patients.Materials and methods Case-control study was conducted on 200 subjects. Four groups were included in the study: A) healthy control group, B) chronic hepatitis C (CHC) non-cirrhotic group, C) CHC-cirrhotic group and, D) CHC-HCC group. Peripheral blood detection of LCSC markers (CD133&CD44) was done by Flow-cytometer analysis, and ELISA was used to detect CAFs markers as Collagen Type XI Alpha I Chain (COL11A1) and α-smooth muscle actin (α-SMA). Results and conclusionSignificant difference in the level of CD133, CD44 and COL11A1 in CHC patients compared to control group (<0.001). Level of previous markers was increased with progression of disease. However, α-SMA level decreased in cirrhotic and HCC groups. Sensitivity of CD133 was 77.78% with specificity 88.24% followed by COL11A1 with higher sensitivity of 83.33%, but a slightly lower specificity of 73.33%. So, CD133 merged as the most promising diagnostic marker for HCC, followed by COL11A1. Regular detection of CSCs and CAFs in circulation may aid in diagnosis and prognosis of liver cirrhosis and HCC.