Abstract 3111: Expression of chromobox homolog 7 (Cbx7) is associated with poor prognosis in ovarian clear cell adenocarcinoma via regulating TRAIL-induced apoptotic pathway.

Abstract

Abstract Ovarian cancer is the most lethal gynecologic malignancy, and among them, clear cell adenocarcinoma of the ovary (OCCA) has relatively worse prognosis associated with chemoresistancy. Chromobox (Cbx) 7 is a component of the polycomb repressive complex 1 that prolongs the lifespan of normal human cells via down-regulating the expression of INK4a/ARF and thus related with cell-cycle progression. However, recent reports studying the relationship between Cbx7 expression and the patient's survival differs among the cell origins of the tumors, and the precise role of Cbx7 in human carcinomas remains obscure. In this study, we analyzed the expression of Cbx7 by immunohistochemistry in 81 OCCA patients and evaluated the association with their clinical outcome. Both overall survival and progression-free survival of the patients were significantly shorter in Cbx7-positive than Cbx7-negative (P<0.05) tumors in OCCA. Cbx7 knockdown experiments using two OCCA cell lines, TOV21G and KOC-7C, revealed that the viability of the cells were significantly reduced compared to control (P<0.001). Expression microarray analysis revealed that apoptosis-related genes, especially TRAIL, were significantly upregulated in Cbx7 knockdown cells (P<0.01). We further confirmed that Cbx-7 knockdown resulted in TRAIL-induced apoptosis in OCCA cells. Thus, in this study, we showed for the first time that Cbx7 is associated with worse prognosis in OCCA. We also successfully demonstrated that the TRAIL pathway is a novel target of Cbx7 in these cells, and therapeutic agents utilizing the TRAIL pathway may be specifically effective targeting OCCA. Citation Format: Yoriko Yamashita, Kanako Shinjo, Eiko Yamamoto, Shinya Akatsuka, Takashi Takahashi, Hiroaki Kajiyama, Fumitaka Kikkawa, Shinya Toyokuni. Expression of chromobox homolog 7 (Cbx7) is associated with poor prognosis in ovarian clear cell adenocarcinoma via regulating TRAIL-induced apoptotic pathway. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3111. doi:10.1158/1538-7445.AM2013-3111 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.