title: Detection of Novel Genomic Markers for Predicting Prognosis in Hepatocellular Carcinoma Patients by Integrative Analysis of Copy Number Aberrations and Gene Expression Profiles: Results from a Long-Term Follow-Up.
abstract: The aim of this study was to explore novel genomic biomarkers predicting hepatocellular carcinoma (HCC) prognosis by integrative analysis of DNA copy number aberrations (CNAs) and gene expression profiles. Array comparative genomic hybridization and expression array were performed on 45 and 31 HCC samples, respectively. To identify functionally important genes, concordant results of DNA copy number and gene expression were retrieved by integrative analysis. Cox regression analysis indicated that the CNAs in 192 genomic regions were significantly associated with overall survival (OS; p < 0.05). Integrative analysis capturing concordant results demonstrated that the low expression of TLE4 (p = 0.041) and XPA (p = 0.006) was associated with poor OS. In the analysis of tumor recurrence, 514 genomic regions with CNAs were associated with recurrence. Integrative analysis revealed that the overexpression of 16 genes, including FGR (p = 0.003), RELA (p = 0.049), LTBP3 (p = 0.050), and RIN1 (p = 0.023), was significantly associated with shorter time to tumor recurrence. On multivariate analysis, FGR and XPA were independent risk factors of early recurrence and poor OS, respectively. Integrated analysis of CNAs and gene expression profiles correlated with long-term follow-up data successfully identified potential prognostic markers predicting survival and tumor recurrence in patients with HCC who underwent surgical resection.
authors.affiliation: 1 Department of Gastroenterology, Ajou University School of Medicine , Suwon, Republic of Korea.
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: 1 Department of Gastroenterology, Ajou University School of Medicine , Suwon, Republic of Korea.
authors.forename: Soon Sun
authors.initials: SS
authors.lastname: Kim
authors.affiliation: 2 Department of Surgery, Ajou University School of Medicine , Suwon, Republic of Korea.
authors.forename: Hee Jeong
authors.initials: HJ
authors.lastname: Wang
authors.affiliation: 2 Department of Surgery, Ajou University School of Medicine , Suwon, Republic of Korea.
authors.forename: Bong Wan
authors.initials: BW
authors.lastname: Kim
authors.affiliation: 3 Department of Biochemistry and Molecular Biology, Ajou University School of Medicine , Suwon, Republic of Korea.|4 Genomic Instability Research Center, Ajou University School of Medicine , Suwon, Republic of Korea.
authors.forename: Hyeseong
authors.initials: H
authors.lastname: Cho
authors.affiliation: 5 Department of Bioinformatics, Macrogen, Inc. , Seoul, Republic of Korea.
authors.forename: Junghee
authors.initials: J
authors.lastname: Jung
authors.affiliation: 5 Department of Bioinformatics, Macrogen, Inc. , Seoul, Republic of Korea.
authors.forename: Samuel Sunghwan
authors.initials: SS
authors.lastname: Cho
authors.affiliation: 6 Department of Radiology, Ajou University School of Medicine , Suwon, Republic of Korea.
authors.forename: Jai Keun
authors.initials: JK
authors.lastname: Kim
authors.affiliation: 6 Department of Radiology, Ajou University School of Medicine , Suwon, Republic of Korea.
authors.forename: Jei Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: 7 Department of Pathology, Ajou University School of Medicine , Suwon, Republic of Korea.
authors.forename: Young Bae
authors.initials: YB
authors.lastname: Kim
authors.affiliation: 1 Department of Gastroenterology, Ajou University School of Medicine , Suwon, Republic of Korea.
authors.forename: Min Jae
authors.initials: MJ
authors.lastname: Yang
authors.affiliation: 1 Department of Gastroenterology, Ajou University School of Medicine , Suwon, Republic of Korea.
authors.forename: Byung Moo
authors.initials: BM
authors.lastname: Yoo
authors.affiliation: 1 Department of Gastroenterology, Ajou University School of Medicine , Suwon, Republic of Korea.
authors.forename: Kwang Jae
authors.initials: KJ
authors.lastname: Lee
authors.affiliation: 1 Department of Gastroenterology, Ajou University School of Medicine , Suwon, Republic of Korea.
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Cho
authors.affiliation: 1 Department of Gastroenterology, Ajou University School of Medicine , Suwon, Republic of Korea.
authors.forename: Jae Youn
authors.initials: JY
authors.lastname: Cheong
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D053779:Latent TGF-beta Binding Proteins / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051996:Transcription Factor RelA / Q000235:genetics; D019061:src-Family Kinases / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; C509038:LTBP3 protein, human; D053779:Latent TGF-beta Binding Proteins; D011518:Proto-Oncogene Proteins; C498143:RELA protein, human; C092117:RIN1 protein, human; D051996:Transcription Factor RelA; C053102:proto-oncogene proteins c-fgr; D019061:src-Family Kinases