title: Hepatic cancer stem cell marker granulin-epithelin precursor and β-catenin expression associate with recurrence in hepatocellular carcinoma.
abstract: Granulin-epithelin precursor (GEP) has been demonstrated to confer enhanced cancer stem-like cell properties in hepatocellular carcinoma (HCC) cell line models in our previous studies. Here, we aimed to examine the GEP-expressing cells in relation to the stem cell related molecules and stem-like cell properties in the prospective HCC clinical cohort. GEP protein levels were significantly higher in HCCs than the paralleled non-tumor liver tissues, and associated with venous infiltration. GEPhigh cells isolated from clinical HCC samples exhibited higher levels of stem cell marker CD133, pluripotency-associated signaling molecules β-catenin, Oct4, SOX2, Nanog, and chemodrug transporter ABCB5. In addition, GEPhigh cells possessed preferential ability to form colonies and spheroids, and enhanced in vivo tumor-initiating ability while their xenografts were able to be serially subpassaged into secondary mouse recipients. Expression levels of GEP and pluripotency-associated genes were further examined in the retrospective HCC cohort and demonstrated significant correlation of GEP with β-catenin. Notably, HCC patients with high GEP and β-catenin levels demonstrated poor recurrence-free survival. In summary, GEP-positive HCC cells directly isolated from clinical specimens showed β-catenin elevation and cancer stem-like cell properties.
authors.affiliation: Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China.|Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, China.|Department of Surgery, The University of Hong Kong, Hong Kong, China.
authors.forename: Phyllis F Y
authors.initials: PF
authors.lastname: Cheung
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong, China.|Department of Surgery, Queen Mary Hospital, Hong Kong, China.
authors.forename: Tan To
authors.initials: TT
authors.lastname: Cheung
authors.affiliation: Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China.|Department of Surgery, The University of Hong Kong, Hong Kong, China.
authors.forename: Chi Wai
authors.initials: CW
authors.lastname: Yip
authors.affiliation: Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Linda W C
authors.initials: LW
authors.lastname: Ng
authors.affiliation: Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China.|Department of Surgery, The University of Hong Kong, Hong Kong, China.|School of Biomedical Sciences, The University of Hong Kong, Hong Kong, China.
authors.forename: Sze Wai
authors.initials: SW
authors.lastname: Fung
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong, China.|Department of Surgery, Queen Mary Hospital, Hong Kong, China.
authors.forename: Chung Mau
authors.initials: CM
authors.lastname: Lo
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong, China.
authors.forename: Sheung Tat
authors.initials: ST
authors.lastname: Fan
authors.affiliation: Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China.|Department of Surgery, The University of Hong Kong, Hong Kong, China.|Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Siu Tim
authors.initials: ST
authors.lastname: Cheung
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D015331:Cohort Studies; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D000077153:Progranulins; D034622:RNA Interference; D014183:Transplantation, Heterologous; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D051176:beta Catenin
keywords: cancer stem cells; granulin-epithelin precursor; hepatocellular carcinoma; β-catenin