title: Identification of PEG10 as a progression related biomarker for hepatocellular carcinoma.
abstract: Widespread DNA copy number alterations are well recognized in hepatocellular carcinoma (HCC), although the affected genes expression remained largely undefined. In this study, we performed genome-wide analysis on HCC to examine the relationship between gene copy number and corresponding transcriptional changes. To ensure analysis on a homogenous population of tumor cells, integrative analysis of array-based CGH and expression profilings was performed on 20 HCC cell lines using a 19,200-element cDNA microarray platform. Further validation studies were carried out on a large series of primary HCC tumors and paired adjacent non-malignant liver to ascertain finding. Correlative analyses highlighted 31 candidate genes that manifested both copy gains and gene up-regulations (R2>0.5; p<0.05). Of interest was over-expressed paternally expressed 10 (PEG10) resided within the chromosome region 7q21 that has been implicated in the progression of HCC. Quantitative PCR and qRT-PCR studies verified concurrent genomic gains and over-expression of PEG10 in HCC cell lines and primary tumors (34/40 cases; 85%). In addition, qRT-PCR demonstrated a significant progressive trend of increasing PEG10 expressions from the putative pre-malignant adjacent livers to early resectable HCC tumors, and to late inoperable HCCs (p=0.007). In summary, the present study demonstrated the usefulness of integrated genomic and expression profilings in identifying candidate genes within regions of genomic alteration. Our results also suggested that PEG10 may be a potential biomarker in the progressive development of HCC, and that genomic gain represents one of the major mechanisms in the induction of PEG10 over-expressions.
authors.affiliation: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
authors.forename: Wai-Ki
authors.initials: WK
authors.lastname: Ip
authors.forename: Paul B-S
authors.initials: PB
authors.lastname: Lai
authors.forename: Navy L-Y
authors.initials: NL
authors.lastname: Wong
authors.forename: Shirley M-H
authors.initials: SM
authors.lastname: Sy
authors.forename: Ben
authors.initials: B
authors.lastname: Beheshti
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Squire
authors.forename: Nathalie
authors.initials: N
authors.lastname: Wong
mesh_terms: D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D017931:DNA Primers; D004268:DNA-Binding Proteins; D018450:Disease Progression; D020869:Gene Expression Profiling; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D017931:DNA Primers; D004268:DNA-Binding Proteins; C432965:PEG10 protein, human; D011506:Proteins; D016601:RNA-Binding Proteins