Evaluation of CD44 and CD133 as markers of liver cancer stem cells in Egyptian patients with HCV-induced chronic liver diseases versus hepatocellular carcinoma

Abstract

BackgroundCancer stem cells (CSCs) play a critical role in tumor development, progression, metastasis and recurrence.AimTo evaluate hepatic expression of CD44 and CD133 in Egyptian patients with HCV-induced chronic liver diseases and hepatocellular carcinomas (HCCs), and to assess its correlation with inflammatory activity scores, stages of fibrosis (in chronic hepatitis with or without cirrhosis) and grades of HCC.MethodsThis prospective case-control study was conducted on eighty subjects who attended the Tropical Diseases Department, Al-Azhar University Hospital, and in collaboration with Theodor Bilharz Research Institute (2014–2016). They were divided as follows: A) Control healthy group: Ten individuals with serologically negative HCV-Ab and HBsAg, and histopathologically normal liver, B) Seventy patients subdivided into 3 groups; Twenty subjects each, as: HCV-Ab+ non-cirrhotic, HCV-Ab+ cirrhotic and HCC. Necroinflammatory activity and fibrosis in non-neoplastic liver biopsies were scored according to the METAVIR scoring system. CD44 and CD133 immunostaining was evaluated in all groups semi-quantitatively using H score. Statistical analysis was performed by SPSS version 22, using independent-samples t-test.ResultsOur study showed a significant increase of mean CD44 & CD133 expression values with disease progression among the groups (p<0.05). Their expressions increased significantly with the inflammatory activity scores and stages of fibrosis, reaching the highest values in A3F4 score compared to A1F1 (p<0.05). Moreover, there was a significant increase of their expressions across HCC grades (p<0.05), however with no significant correlation with focal lesions size.ConclusionCSCs clusters exhibiting CD133+ and/or CD44+ profiles were identified in chronic hepatitis, liver cirrhosis and HCC. CD133 and CD44 expressions significantly corresponded to the increased inflammatory activity, fibrosis stages and higher tumor grades. Therefore, evaluation of CD44 and CD133 expression profiles as CSCs markers in non-neoplastic liver and HCCs can help in development of novel therapeutic agents for HCC targeting and prevention.

Liver Fibrosis and Inflammation under the Control of ERK2

“…Moreover, CD44 is a cancer stem cell marker and mediates signaling pathways for tumor differentiation, invasion, and metastasis [43]. The CD44 and CD133 expression increased with the grades of inflammation and stages with fibrosis upon virus infection [44]. The expression of CD133 was down-regulated in Erk2 −/− livers when compared to WT livers in this study.…”

Potentiation of TRAIL‑induced cell death by nonsteroidal anti‑inflammatory drug in human hepatocellular carcinoma cells through the ER stress‑dependent autophagy pathway

“…Expression of CD44 and CD133 as markers of liver cancer stem cells can contribute to hepatocellular carcinoma (HCC) development and poor responsiveness of HCC towards chemotherapy and radiotherapy ( 18 ). Since high susceptibility to TRAIL of HCC cells is associated with CD133 expression ( 19 ), we therefore investigated whether the acquisition of resistance to TRAIL is associated with distribution of CD44/CD133 expression in HCC cells.…”

“…The CSC population in HCC can be responsible for metastasis, recurrence and chemoresistance of HCC ( 40 ). In HCC, markers most frequently used for CSC are CD44 and CD133 ( 18 ), and particularly CD44 expression was reported to be correlated with high HCC histologic grades, vascular invasion, and reduced survival outcomes ( 41 ). Another potential CSC marker is CD133 that is released from the plasma membrane to the cytoplasm, and overexpression of CD133 constitutively activates autophagy via inhibition of mTORC1 and mTORC2 signaling and potentiation of autophagy flux ( 42 ).…”

Ultrasound-Targeted Microbubble Destruction-Mediated Downregulation of EZH2 Inhibits Stemness and Epithelial-Mesenchymal Transition of Liver Cancer Stem Cells

“…24,25 Some characteristic surface antigens have been found present on CSCs, such as CD13, CD44, and CD133. 26,27 It was reported that CD133 was widely expressed in leukemia, liver cancer, lung cancer, prostate cancer and other CSCs, and could be used to identify and isolate a variety of CSCs including liver CSCs. 28 CD133 functions as an important marker for CSCs, and has been proved to be closely related to the occurrence, development and prognosis of cancers.…”