Tomohiko Sakabe1,2, Junya Azumi1, Yoshihisa Umekita2, Kan Toriguchi3, Etsuro Hatano3, Yasuaki Hirooka4, Goshi Shiota1. 1. Division of Molecular and Genetic Medicine, Department of Medicine and Regenerative Therapeutics, Graduate School of Medicine, Tottori University, Yonago, Japan. 2. Division of Organ Pathology, Department of Pathology, Faculty of Medicine, Tottori University, Yonago, Japan. 3. Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. 4. Department of Pathobiological Science and Technology, School of Health Science, Faculty of Medicine, Tottori University, Yonago, Japan.
Abstract
BACKGROUND & AIMS: Cancer stem cells (CSCs) play a pivotal role in progression, metastasis and recurrence of cancer. Therefore, it is clinically useful to identify the relevant CSC marker that is associated with prognosis of hepatocellular carcinoma (HCC) and clarify its genetic and biological characteristics. METHODS: Expression of four CSC markers, CD13, EpCAM, CD44 and CD44v9, was examined in 99 HCC patients. Biological and cDNA/miRNA microarray data were compared among CD44-positive/-negative HCC cells and normal hepatic cells. The significance of the representative miRNAs was examined with regard to prognosis of additional 110 HCC patients. RESULTS: CD44-positive HuH7 cells proliferated faster and showed a greater sphere forming ability than CD44-negative HuH7 cells. CD44-positive HuH7 cells exhibited higher expression of specific genes involved in resistance to reactive oxygen species, anticancer drugs and tumour invasion than CD44-negative HCC cells. Higher expression of six miRNAs was observed in CD44-positive HuH7 cells, CD44-negative HuH7 cells, and human normal hepatic cells in that order. Of the six miRNAs, miR-137 was closely associated with overall and cancer-specific survivals, as well as with invasion of hepatic vein, hepatic artery, portal vein and bile duct, and alpha-foetoprotein in additional 110 HCC patients. CONCLUSIONS: miR-137 may serve as a prognostic marker in patients with HCC and may be a potential target for the elimination of liver CSCs.
BACKGROUND & AIMS:Cancer stem cells (CSCs) play a pivotal role in progression, metastasis and recurrence of cancer. Therefore, it is clinically useful to identify the relevant CSC marker that is associated with prognosis of hepatocellular carcinoma (HCC) and clarify its genetic and biological characteristics. METHODS: Expression of four CSC markers, CD13, EpCAM, CD44 and CD44v9, was examined in 99 HCC patients. Biological and cDNA/miRNA microarray data were compared among CD44-positive/-negative HCC cells and normal hepatic cells. The significance of the representative miRNAs was examined with regard to prognosis of additional 110 HCC patients. RESULTS:CD44-positive HuH7 cells proliferated faster and showed a greater sphere forming ability than CD44-negative HuH7 cells. CD44-positive HuH7 cells exhibited higher expression of specific genes involved in resistance to reactive oxygen species, anticancer drugs and tumour invasion than CD44-negative HCC cells. Higher expression of six miRNAs was observed in CD44-positive HuH7 cells, CD44-negative HuH7 cells, and human normal hepatic cells in that order. Of the six miRNAs, miR-137 was closely associated with overall and cancer-specific survivals, as well as with invasion of hepatic vein, hepatic artery, portal vein and bile duct, and alpha-foetoprotein in additional 110 HCC patients. CONCLUSIONS:miR-137 may serve as a prognostic marker in patients with HCC and may be a potential target for the elimination of liver CSCs.
Authors: Hamdy E A Ali; Ahmed A Emam; Ahmed A Zeeneldin; Reham Srour; Reda Tabashy; Eman D El-Desouky; Zakaria Y Abd Elmageed; Abdel-Hady A Abdel-Wahab Journal: Clin Biochem Date: 2019-01-15 Impact factor: 3.281