Stemness-related transcriptional factors and homing gene expression profiles in hepatic differentiation and cancer.
Stem cell transcriptional signature activation is an essential event in the development of cancer. This study aimed to investigate the differential expression profile of three pluripotency-associated genes (OCT4,NANOG, andSOX2), G-protein-coupled chemokine receptor 4 (CXCR4) and the ligand (CXCL2), and alpha feto-protein (AFP) in hepatogenic differentiated stem cells and in sera of hepatitis C virus (HCV) and HCV-induced hepatocellular carcinoma (HCC) patients. Mesenchymal stem cells derived from umbilical cord blood were differentiated using hepatogenic differentiation media. Serum specimens were collected from 96 patients (32 cirrhotic HCV, 32 early HCC, and 32 late HCC) and 96 controls. Real-time quantitative reverse transcription polymerase chain reaction was performed for relative quantification of the 6 target genes using LIVAC method.In siliconetwork analysis was also executed to explore the pluripotency and tumorigenic regulatory circuits in liver cancer. The expression levels of all genes declined gradually during the stages of stem cell differentiation. On univariate and multivariate analyses,NANOG,CXCR4andAFPwere significantly up-regulated in HCC patients with late clinical stage. In contrast,SOX2andCXCL2were markedly over-expressed in cirrhotic patients and could be used for clear demarcation between cirrhotic and HCC patients in our cases. In conclusion, our data highlight the potential role ofSOX2stem cell marker andCXCL2chemokine in liver cell degeneration and fibrogenesis in HCV-induced hepatic cirrhosis in our sample of the Egyptian population. In addition, the significant association ofNANOGandCXCR4high-expression with late HCC, could contribute to the acquisition of stem cell-like properties in hepatic cancer and dissemination in late stages, respectively. Taken together, our results could have a potential application in HCC prognosis and treatment.
Department of Histology and Cell Biology, Genetics Unit, Faculty of Medicine, Suez Canal University, Ismailia, Egypt, P.O. 41522.
Eman A
EA
Toraih
Department of Medical Biochemistry, Faculty of Medicine, Suez Canal University, Ismailia, Egypt, P.O. 41522.
Manal S
MS
Fawzy
Biotechnology Research Center, Suez Canal University, Ismailia, Egypt.
Abdullah I
AI
El-Falouji
Clinical Pathology Department, Faculty of Medicine, Sohag University, Sohag, Egypt.
Elham O
EO
Hamed
Endemic and Infectious diseases Department, Suez Canal University, Ismailia, Egypt.
Nader A
NA
Nemr
Pulmonologist, Ministry of Health, Egypt.
Mohammad H
MH
Hussein
Department of Medical Biochemistry, Faculty of Medicine, Suez Canal University, Ismailia, Egypt, P.O. 41522.
Noha M
NM
Abd El Fadeal
Real-time qPCR; chemokines; hepatocellular carcinoma; liver cirrhosis; pluoripotent genes