Abstract 3173: Clinical significance of Fanconi anemia complementation group E(FANCE)DNA repair-related gene expression in hepatocellular carcinoma

Abstract

Abstract Background : Hepatocellular carcinoma (HCC) is one of the most threatening malignancies because of the limited availability of radical therapeutic options. Thus, identification of prognostic biomarkers as well as molecular therapeutic targets of HCC should be very important for HCC patients. Fanconi anemia complementation group E (FANCE) is a DNA repair-related gene and it’s deletion is one of causes of Fanconi anemia. Recent studies reported that FANCD2 which is activated by FA complex involving FANCE shows high expression in HCC and expression of FANCD2 is in direct proportion to the grade of malignancy of HCC (Anticancer Res, 2017). And other studies reported that FANCE shows high expression in breast cancer (J Mol Biol, 2015). However clinical significance of FANCE expression in HCC is unknown. Objective : To clarify the clinical significance of FANCE expression in HCC. Material and method: Firstly, we assessed the relation between mRNA expression of FANCE and prognosis using large scale HCC gene data sets (The Cancer Genome Atlas; TCGA, Gene Expression Omnibus; GEO, and European Genome-phenome Archive; EGA). Secondly, the mRNA expression of FANCE was measured in 72 surgically resected HCC in our hospital during the period from 2000 to 2004 by RT-qPCR (normalized by internal control GAPDH), and we compared the expression of FANCE in between tumors and normal tissues. Thirdly, we assessed the associations between expression of FANCE and clinicopathological factors. Finally, we investigated the localization of FANCE by immunohistochemical staining data of THE HUMAN PROTEIN ATLAS. Result: In large scale HCC gene data sets and our samples, tumor tissues have higher mRNA expression of FANCE than normal tissues(t test. p<0.001). The high expression of FANCE was significantly associated with poor prognosis (Kaplan-Meier method, Log rank test. p<0.05). In the clinicopathological analysis, FANCE expression was not associated with any clinicopathological factors except age (p<0.05). THE HUMAN PROTEIN ATLAS showed that FANCE is expressed in the nuclei of HCC cells. Discussion: FANCE was overexpressed in HCC cells, and the high expression of FANCE was associated with poor prognosis. So high expression of FANCE could be a prognostic biomarker in HCC. Now we are performing knockdown experiment for FANCE to clarify the biological significance of FANCE expression in HCC.Conclusion: FANCE could be a prognostic biomarker in HCC. Citation Format: Junichi Takahashi, Takaaki Masuda, Yosuke Kuroda, Akihiro Kitagawa, Yushi Motomura, Kensuke Koike, Dai Shimizu, Shotaro Kuramitsu, Atsushi Fujii, Miwa Noda, Kuniaki Sato, Yusuke Tsuruda, Hajime Otsu, Hidetoshi Eguchi, Keishi Sugimachi, Masaki Mori, Koshi Mimori. Clinical significance of Fanconi anemia complementation group E(FANCE)DNA repair-related gene expression in hepatocellular carcinoma [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 3173.