Diagnostic value of miR-203 and its target genes (survivin and cyclin D) in circulating liver cancer stem cells for detection of hepatocellular carcinoma: a case–control study in Egyptian patients with chronic hepatitis C

Hepatocellular carcinoma (HCC) is the 6th most frequent malignant tumor globally. Egypt is the second highest country regarding HCC prevalence and is related to a past hepatitis C virus (HCV) infection. HCC surveillance in high-risk populations is crucial with the use of ultrasound and sometimes alpha-fetoprotein. Alpha-fetoprotein is still used, although it has suboptimal sensitivity. The aim of this research is to evaluate the expression of miR-203 and its target genes (survivin and cyclin D) levels in circulating liver cancer stem cells (LCSC) in patients with chronic HCV with and without HCC. This study was a case–control study. It included eighty participants. They were categorized into 4 groups. Twenty cases were included in the group with chronic HCV. Another 20 patients were included in the group with HCV liver cirrhosis. The third group included 20 patients with HCC related to HCV infection. Twenty normal subjects, age- & sex-matched, were assigned as a control group. The expressions of miR-203, survivin, and cyclin D were measured by using quantitative real-time PCR in patients’ serum samples from LCSC-positive fractions. miR-203 demonstrated the highest diagnostic accuracy in differentiating HCV-related cirrhotic patients with HCC from those without HCC, with an AUC of 0.974 [95% CI 0.86–0.99] at a cut-off of ≤ 1.32, achieving both excellent sensitivity (100%) and specificity (95%). Survivin at a cut-off > 4.52 showed good diagnostic performance with an AUC of 0.851 (95% CI: 0.70–0.94) with high specificity (95%) and moderate sensitivity (70%). Cyclin-D, using a cut-off value > 1.78, yielded an AUC of 0.85 (95% CI: 0.63–0.95) with high sensitivity (100%) but moderate specificity (85%). The current study highlights the clinical utility of miR-203 and its target genes, survivin and cyclin-D, in the diagnosis of HCC related to HCV infection. It showed that miR-203 was superior to its target genes. Both survivin and cyclin D could be complementary for detection of HCC. More research is required to assess the efficiency of these biomarkers in various clinical settings and their correlation with the stages of HCC and the recurrence of HCC in transplanted patients.