title: Downregulation of PLZF in human hepatocellular carcinoma and its clinical significance.
abstract: Promyelocytic leukemia zinc finger (PLZF) acts as a tumor-suppressor gene in a series of cancers including prostate, melanoma, colon cancer and leukemia. However, its role in hepatocellular carcinoma (HCC) has not yet been illustrated. The present study aimed to investigate the expression and epigenetic regulation of PLZF as well as its clinical significance in HCC. We found that the expression of PLZF was significantly downregulated in HCC samples at both the RNA level (P<0.001) and protein level compared with these levels in adjacent normal tissues. The relative expression level of PLZF was also positively correlated with the ALP level (P=0.026) noted in the HCC patients. However, hypermethylation was only detected in one out of 5 paired HCC samples, indicating that methylation of the selected promoter region (from -1702 to -1388) may not be the major regulatory mechanism for the downregulation of PLZF in HCC. A receiver operating characteristic (ROC) curve was created to evaluate the diagnostic value for differentiating between HCC and benign diseases. The area under the ROC curve (AUC) for indicating the value of PLZF as an HCC biomarker was 0.794 (95% CI, 0.697-0.892; P<0.001). Taken together, our results suggest that PLZF may play an important role in HCC development and may be a potential biomarker for the diagnosis of HCC.
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, SAR, P.R. China.
authors.forename: Anselm Wang-Hei
authors.initials: AW
authors.lastname: Hui
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, SAR, P.R. China.
authors.forename: Hon-Wai
authors.initials: HW
authors.lastname: Lau
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, SAR, P.R. China.
authors.forename: Cyanne Ye
authors.initials: CY
authors.lastname: Cao
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, SAR, P.R. China.
authors.forename: Jun-Wei
authors.initials: JW
authors.lastname: Zhou
authors.affiliation: Department of Surgery, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, SAR, P.R. China.
authors.forename: Paul Bo-San
authors.initials: PB
authors.lastname: Lai
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, SAR, P.R. China.
authors.forename: Stephen Kwok-Wing
authors.initials: SK
authors.lastname: Tsui
mesh_terms: D000368:Aged; D000469:Alkaline Phosphatase / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D019175:DNA Methylation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D012372:ROC Curve; D012016:Reference Values
chemical_list: D014408:Biomarkers, Tumor; D051741:Kruppel-Like Transcription Factors; D000075722:Promyelocytic Leukemia Zinc Finger Protein; C092037:ZBTB16 protein, human; D000469:Alkaline Phosphatase