PSMB8 and PBK as potential gastric cancer subtype-specific biomarkers associated with prognosis.

// Chae Hwa Kwon 1 , Hye Ji Park 1 , Yu Ri Choi 1 , Ahrong Kim 1 , Hye Won Kim 1 , Jin Hwa Choi 1 , Chung Su Hwang 1 , So Jung Lee 1 , Chang In Choi 2 , Tae Yong Jeon 2 , Dae Hwan Kim 2 , Gwang Ha Kim 3 and Do Youn Park 1 1 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 2 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 3 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 Correspondence to: Do Youn Park, email: // Keywords : stomach, adenocarcinoma, prognosis, PSMB8, PBK Received : August 10, 2015 Accepted : February 05, 2016 Published : February 15, 2016 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 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.