title: PSMB8 and PBK as potential gastric cancer subtype-specific biomarkers associated with prognosis.
abstract: Gastric adenocarcinoma is a common form of cancer associated with a poor prognosis. We analyzed microarray profiling data from 48 patients with gastric adenocarcinoma to characterize gastric cancer subtypes and identify biomarkers associated with prognosis. We identified two major subtypes of gastric adenocarcinoma differentially associated with overall survival (P = 0.025). Genes that were differentially expressed were identified using specific criteria (P < 0.001 and >1.5-fold); expression of 294 and 116 genes was enriched in good and poor prognosis subtypes, respectively. Genes related to translational elongation and cell cycle were upregulated in the poor prognosis group. Of these genes, upregulation of proteasome subunit beta type 8 PSMB8 and PDZ binding kinase PBK was confirmed by real-time reverse transcription-PCR analysis. PSMB8 or PBK knockdown had no effect on gastric cancer cell proliferation but suppressed cell migration and invasion, respectively. Furthermore, immunohistochemistry analysis of 385 gastric cancer patients revealed that increased nuclear expression of PSMB8 and PBK was correlated with depth of invasion, lymph node metastasis, and lower survival rates. Taken together, two gastric adenocarcinoma subtypes were predictive of prognosis. PSMB8 and PBK were predictive of gastric cancer prognosis and could be potential gastric cancer subtype-specific biomarkers.
authors.affiliation: Department of Pathology, Pusan National University Hospital and Pusan National University School of Medicine, and BioMedical Research Institute, Pusan National University Hospital, Seo-Gu, Busan, Korea.
authors.forename: Chae Hwa
authors.initials: CH
authors.lastname: Kwon
authors.affiliation: Department of Pathology, Pusan National University Hospital and Pusan National University School of Medicine, and BioMedical Research Institute, Pusan National University Hospital, Seo-Gu, Busan, Korea.
authors.forename: Hye Ji
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Department of Pathology, Pusan National University Hospital and Pusan National University School of Medicine, and BioMedical Research Institute, Pusan National University Hospital, Seo-Gu, Busan, Korea.
authors.forename: Yu Ri
authors.initials: YR
authors.lastname: Choi
authors.affiliation: Department of Pathology, Pusan National University Hospital and Pusan National University School of Medicine, and BioMedical Research Institute, Pusan National University Hospital, Seo-Gu, Busan, Korea.
authors.forename: Ahrong
authors.initials: A
authors.lastname: Kim
authors.affiliation: Department of Pathology, Pusan National University Hospital and Pusan National University School of Medicine, and BioMedical Research Institute, Pusan National University Hospital, Seo-Gu, Busan, Korea.
authors.forename: Hye Won
authors.initials: HW
authors.lastname: Kim
authors.affiliation: Department of Pathology, Pusan National University Hospital and Pusan National University School of Medicine, and BioMedical Research Institute, Pusan National University Hospital, Seo-Gu, Busan, Korea.
authors.forename: Jin Hwa
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Department of Pathology, Pusan National University Hospital and Pusan National University School of Medicine, and BioMedical Research Institute, Pusan National University Hospital, Seo-Gu, Busan, Korea.
authors.forename: Chung Su
authors.initials: CS
authors.lastname: Hwang
authors.affiliation: Department of Pathology, Pusan National University Hospital and Pusan National University School of Medicine, and BioMedical Research Institute, Pusan National University Hospital, Seo-Gu, Busan, Korea.
authors.forename: So Jung
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Surgery, Pusan National University Hospital and Pusan National University School of Medicine, and BioMedical Research Institute, Pusan National University Hospital, Seo-Gu, Busan, Korea.
authors.forename: Chang In
authors.initials: CI
authors.lastname: Choi
authors.affiliation: Department of Surgery, Pusan National University Hospital and Pusan National University School of Medicine, and BioMedical Research Institute, Pusan National University Hospital, Seo-Gu, Busan, Korea.
authors.forename: Tae Yong
authors.initials: TY
authors.lastname: Jeon
authors.affiliation: Department of Surgery, Pusan National University Hospital and Pusan National University School of Medicine, and BioMedical Research Institute, Pusan National University Hospital, Seo-Gu, Busan, Korea.
authors.forename: Dae Hwan
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Pusan National University Hospital and Pusan National University School of Medicine, and BioMedical Research Institute, Pusan National University Hospital, Seo-Gu, Busan, Korea.
authors.forename: Gwang Ha
authors.initials: GH
authors.lastname: Kim
authors.affiliation: Department of Pathology, Pusan National University Hospital and Pusan National University School of Medicine, and BioMedical Research Institute, Pusan National University Hospital, Seo-Gu, Busan, Korea.
authors.forename: Do Youn
authors.initials: do Y
authors.lastname: Park
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D046988:Proteasome Endopeptidase Complex / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D020929:Mitogen-Activated Protein Kinase Kinases; C409022:PDZ-binding kinase; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex
keywords: PBK; PSMB8; adenocarcinoma; prognosis; stomach