Overexpression of DEK in human gastric carcinoma and its clinicopathological significance.

Abstract

75 Background: Gastric cancer (GAC) is the second most common cancer worldwide and the fifth leading cause of cancer-related death in Taiwan. To improve the survival of gastric cancer patients, biomarkers for early detection and effective anticancer therapy are required. Methods: Dysregulated proteins in GAC tumor cells were captured and identified by laser capture microdissection (LCM) and an isobaric tags for relative and absolute quantitation (iTRAQ)-labeling following basic-RP HPLC coupled to LTQ-orbitrap MS analysis. DEK, one of the most highly-expressed proteins in both intestinal and diffuse gastric cancers in iTRAQ analysis, was selected for further study. DEK proto-oncogene is originally identified as a fusion with the CAN nucleoporin protein in a subset of acute myeloid leukemia (AML) patients carrying the t(6;9) translocation, and DEK has been implicated in acute myeloid leukemia, melanoma, glioblastoma, hepatocellular carcinoma, and bladder cancer. The overexpression of DEK was confirmed using real-time quantitative-reverse transcription-polymerase chain reaction (Q-RT–PCR), Western blot, and immunohistochemical (IHC) analysis. Results: The data revealed that the expression of DEK mRNA was up-regulated in tumor tissues (compared with adjacent non-tumor tissues) of about 55.1% gastric patients. The expression of DEK protein was also up-regulated in tumor tissues identified by Western blot and IHC. To further understand the role of DEKgene in the human gastric cancer cells, the DEK knockdown stable clones were prepared in AZ521. The cells migration ability was reduced in DEK depletion stable clones, and the antitumor drug sensitivity and anoikis were increased in DEK depletion cells. Conclusions: These results indicate that DEK overexpression may contribute the poor prognosis of patients.