Study of Cancer Stem Cells (CSCs) in Hepatitis C Virus (HCV) - Associated Hepatocellular Carcinoma Patients: Links to Diagnosis and Prognosis

Introduction: As the sixth most common cancer worldwide, hepatocellular carcinoma (HCC) represents about 90% of all primary liver cancers, thereby accounting for 485,000 deaths as of 2019. Advancement of the carcinogenic process, as well as resistance of different tumors to various lines of therapy, can be largely attributed to a subpopulation of tumor cells, known as cancer stem cells (CSCs), capable of growth, differentiation, and self-renewal. CSCs are considered tumor cells that have been sloughed from the primary tumor and are swept away into the general circulation, thus promoting tumor metastasis. Numerous markers have been used to identify different CSCs, but none of these tested markers have been found to be universally expressed in all neoplasms. Nevertheless, CD45 ^- , CD90 ⁺ , CD133 ⁺ , and cytokeratin (CK) 19 have been evaluated in hepatocellular carcinoma (HCC). Aim of the study: To assess the role of CD45 ^- , CD90 ⁺ , CD133 ⁺ , and CK19 as markers of CSCs in diagnosis and prognosis of HCC in hepatitis C virus (HCV) patients. Subjects and methods: This prospective case-control study was conducted over a period of four years from 2020 to 2024 and included 95 subjects classified into 3 groups. Group A consisted of 50 patients who developed HCC on top of HCV-induced liver cirrhosis while Group B comprised 30 patients with post-HCV liver cirrhosis and Group C included 15 healthy controls. Flowcytometry was used to detect CSCs in each participant using 5 ml venous blood. Results: CD45 ^- , CD90 ⁺ , CD133 ⁺ , and CK19 ⁺ cells were significantly elevated in HCC patients compared to both cirrhotic and control groups ( P ≤0.001). Within the HCC patient group, these four cell types were all higher in those with vascular invasion, while only CD45 ^- , CD90 ⁺ , and CK19 ⁺ cells were elevated in patients with larger tumors. Furthermore, evaluation of CSCs markers in relation to treatment response showed that CD45 ^- , CD90 ⁺ , and CD133 ⁺ cells were higher in patients with complete response (CR) when compared to those with progressive disease (PD). Conclusion: CD45 ^- , CD90 ⁺ , CD133 ⁺ , and CK19 as markers of CSCs can be used in both diagnosis of HCC and in evaluating tumor progression.