title: Identification of NUCKS1 as a putative oncogene and immunodiagnostic marker of hepatocellular carcinoma.
abstract: Although the molecular mechanisms underpinning hepatocellular carcinoma (HCC) are unknown, gene copy number and associated mRNA expression changes are frequently reported. Comparative genomic hybridization arrays spotted with 4041 bacterial artificial chromosome clones were used to assess copy number changes in 45 HCC tissues. Seventy more HCC tissues were used to validate candidate genes by using western blots and immunohistochemistry. A total of 259 clones were associated with copy number changes that significantly differed between normal liver and HCC samples. The chromosomal region 1q32.1 containing the nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) gene was associated with tumor vascular invasion. Western blot analysis demonstrated that NUCKS1 was up-regulated in 37 of 70 (52.8%) HCC tissues compared with adjacent non-tumor tissues, and over-expressed in a vast majority of HCCs (44/52, 84.6%) as determined by immunohistochemical staining. Furthermore, immunostaining of both NUCKS1 and glypican-3 improved the diagnostic prediction of HCC. Knock-down of NUCKS1 by siRNA implied the decrease in cell viability of the Hep3B cell line and reduced tumor formation in a xenograft mouse model. NUCKS1 was identified as a potential oncogene at chromosomal 1q32.1 in patients with HCC, and it might be a valuable immunodiagnostic marker for HCC.
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea; Genome Research Center for Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea. Electronic address: jaeyoun620@gmail.com.
authors.forename: Jae Youn
authors.initials: JY
authors.lastname: Cheong
authors.affiliation: Department of Pathology, Ajou University School of Medicine, Suwon, Republic of Korea. Electronic address: ybkim@ajou.ac.kr.
authors.forename: Young Bae
authors.initials: YB
authors.lastname: Kim
authors.affiliation: Macrogen Inc., Seoul, Republic of Korea. Electronic address: hydepark83@gmail.com.
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Woo
authors.affiliation: Genome Research Center for Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea. Electronic address: dkkim75@cj.net.
authors.forename: Dong Kyu
authors.initials: DK
authors.lastname: Kim
authors.affiliation: Genome Research Center for Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea. Electronic address: marie8346@cj.net.
authors.forename: Marie
authors.initials: M
authors.lastname: Yeo
authors.affiliation: Macrogen Inc., Seoul, Republic of Korea. Electronic address: sjyang0901@gmail.com.
authors.forename: Song-Ju
authors.initials: SJ
authors.lastname: Yang
authors.affiliation: Macrogen Inc., Seoul, Republic of Korea. Electronic address: ksyang@macrogen.com.
authors.forename: Kap-Seok
authors.initials: KS
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea; Genome Research Center for Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea. Electronic address: cocorico99@gmail.com.
authors.forename: Sun Kim
authors.initials: SK
authors.lastname: Soon
authors.affiliation: Department of Surgery, Ajou University School of Medicine, Suwon, Republic of Korea. Electronic address: wanghj@ajou.ac.kr.
authors.forename: Hee Jeong
authors.initials: HJ
authors.lastname: Wang
authors.affiliation: Department of Surgery, Ajou University School of Medicine, Suwon, Republic of Korea. Electronic address: drbwkim@ajou.ac.kr.
authors.forename: Bong Wan
authors.initials: BW
authors.lastname: Kim
authors.affiliation: Insilicogen Inc., Suwon, Republic of Korea. Electronic address: jhpark@insilicogen.com.
authors.forename: Jun-Hyung
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea; Genome Research Center for Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea. Electronic address: sung_woncho@hotmail.com.
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Cho
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D002878:Chromosomes, Human, Pair 1; D056915:DNA Copy Number Variations; D020869:Gene Expression Profiling; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D009687:Nuclear Proteins / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C426654:NUCKS1 protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins
keywords: Copy number aberration; Diagnostics; Hepatocellular carcinoma; Immunostaining; NUCKS1