Abstract 475: Clinical significance of eif5-mimic protein 1 in pancreatic cancer

Abstract

Abstract Background: Pancreatic cancer (PC) is the most lethal cancer in humans, with a 5-year survival rate of less than 10%. Thus, identification of prognostic biomarkers as well as molecular therapeutic targets should be critical. Translational reprogramming in cancer has been attracting attention. Several studies have reported that genomic alternations of a translational regulatory gene contributing to malignancy. eIF5-mimic protein 1 (5MP1), previously termed BZW2 is a member of the bZIP superfamily of transcription factors. 5MP1 is reported to be upregulated and has a pro-tumor effect via activation of the Akt/mTOR signaling pathway in osteosarcoma. However, the role and mechanisms of 5MP1 in PC remains unknown. The aim of this study is to clarify the clinical significance of 5MP1 expression in PC. Material and method: Firstly, we analyzed public datasets of PC (178 RNA-sequencing data from The Cancer Genome Atlas, 36 gene expression array data from GSE 15471, 45 gene expression array data from GSE 28735, 69 gene expression array data from GSE 62452, 145 primary PC and 46 normal pancreas gene expression array data from GSE 71729, 45 Copy number variation and expression array data from Broad-Novartis Cancer Cell Line Encyclopedia(CCLE)). Then we performed Gene set enrichment analysis (GSEA) to identify the gene sets which were associated with the expression of 5MP1 in PC. Finally, we investigated the localization of 5MP1 by immunohistochemical staining data of THE HUMAN PROTEIN ATLAS and also confirmed with staining our histological specimens. Results: In tumor tissues, mRNA expression of 5MP1 was higher than normal tissues (t-test. p<0.05). Survival analysis showed high expression of 5MP1 was significantly associated with poor prognosis (Kaplan-Meier method, Log-rank test. p<0.05). Analysis of pancreas cancer cell line CCLE indicated a significant positive correlation between Copy number variation and expression of 5MP1 ( r = 0.41 ). Moreover, GSEA revealed the relationship between enhanced 5MP1 expression and cycle-related gene set. Immunohistochemistry staining showed prominent expression of 5MP1 in the plasma membranes of PC cells. Conclusion and Significance: We demonstrated that 5MP1 was overexpressed in PC cells, and the high expression was associated with poor prognosis. These results suggest that 5MP1 may be associated with tumor progression and can be a promising biomarker for a patient with a poor prognosis of PC. Now we are performing a knockdown experiment for 5MP1 to clarify its biological significance in PC. Citation Format: Yushi Motomura, Takaaki Masuda, Kuniaki Sato, Atsushi Fujii, Akihiro Kitagawa, Hiroaki Wakiyama, Kensuke Koike, Junichi Takahashi, Dai Shimizu, Shotaro Kuramitsu, Miwa Noda, Yusuke Tsuruda, Hajime Otsu, Yosuke Kuroda, Hidetoshi Eguchi, Katsumi Sakamoto, Masakazu Hirakawa, Hiroshi Honda, Koshi Mimori. Clinical significance of eif5-mimic protein 1 in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 475.