Abstract 837: PSMB8 as a candidate marker of responsiveness to preoperative radiotherapy in rectal cancer patients

Abstract

Abstract Prediction of individual responsiveness is urgently needed, specifically in locally advanced rectal cancer (LARC) patients who underwent preoperative chemoradiotherapy (CRT). The present study, RNA-Seq was used to compare the basal expression profile between responders and non-responders to preoperative CRT, in correlation with the tumor regression grade (TRG) among 22 LARC patients. Eight differentially expressed genes (B3GALT4, HSPA1B, KRBOX1, PPBP, PPP1R18, PSMB8, SLC39A7, and TAP2) associated with preoperative CRT responses were primarily identified among the 22 LARC patients by RNA-Seq (p<0.0005 and >16-fold difference). Among these genes, PSMB8 and SLC39A7 were upregulated in the responsive group in the other 40 LARC patients (p<0.05). PSMB8 overexpression significantly reduced colony formation and increased apoptosis-inducing molecules like cleaved caspase-3 and cleaved PARP in irradiated CRC cells after 6 Gy irradiation. PSMB8 knockdown increased colony formation and decreased caspase-3 activation and cleaved PARP levels after irradiation. In mice treated with ionizing radiation, tumor growth suppression was significantly greater in HCT116/PSMB8-xenografts (81%) than in HCT116/vector-xenografts (53%) (p=0.001). However, SLC39A7 overexpression had no significant effect on irradiated CRC cells. These results suggest that PSMB8 appears to predict radiosensitivity in LARC patients with preoperative CRT, although further clinical validation is needed in a larger cohort. Citation Format: Yejin Ha, Ka hee Tak, Chan wook Kim, Seon Ae Roh, Eun Kyung Choi, Dong Hyung Cho, Jeong-Hwan Kim, Seon-Kyu Kim, Seon-Young Kim, Yong Sung Kim, Jin-Cheon Kim. PSMB8 as a candidate marker of responsiveness to preoperative radiotherapy in rectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 837. doi:10.1158/1538-7445.AM2017-837