Abstract 2614: Macrophage erythroblast attacher (MAEA) polymorphisms are associated with clinical outcome in TRIBE study mCRC patients treated with 5-fluorouracil/bevacizumab-based therapy

Abstract

Abstract Background: Macrophage erythroblast attacher (MAEA) also known as Emp (Erythroblast macrophage protein) plays indispensable role in erythroblast and macrophage development and targeted disruption of Emp is embryonically lethal (Soni et al., JBC 2006). Recently, down-regulation of Emp was implicated in abnormal cell motility and higher expression of mitogen-activated protein kinase 1 (MAPK 1) and thymoma viral proto-oncogene 1 (Akt 1) (Gulnaz et. al., BCMD 2016). Our preliminary studies, shows that higher expression of MAEA is associated with longer colorectal cancer (CRC) patient survival. We tested two MAEA polymorphisms (rs13149952 and rs1128427), whether these are correlated with clinical outcome in mCRC treated with 5-Fluorouracil / Bevacizumab based therapy. Methods: Genomic DNA was isolated from blood samples of two cohorts of mCRC patients. Cohort 1 included 227 patients treated with FOLFIRI/BEV (TRIBE trial Arm A, RAS wildtype/mutant=55/116, median age=60 years old, median follow-up period=49.3 months). Cohort 2 had 229 patients treated with FOLFOXIRI/BEV (TRIBE trial Arm B, RAS wildtype/mutant=60/115, median age=60 years old, median follow-up period=46.6 months). PCR-based direct Sanger sequencing was used to determine polymorphism. Results: Our results showed that MAEA rs1128427 in TRIBE arm A patients with RAS mutant tumors having any C genotype was significantly associated with longer overall survival as compared to TT genotype in univariate analysis {25.9 vs 18.8 months, HR(95% CI)=0.61(0.38,0.98), p=0.036}. In TRIBE arm B cohort, MAEA rs1128427 in patients with RAS mutant tumors carrying CC genotype showed significantly longer overall survival than patients with any T allele in both univariate and multivariable analyses {33.4 vs 25 months, uni: HR(95% CI)=0.57(0.34,0.95), p=0.028; multi: HR(95% CI)=0.56(0.32,0.96), p=0.034}. Conclusion: Our findings suggest for the first time, that polymorphisms in MAEA may predict the clinical outcome in Bevacizumab based therapies. Further prospective studies are warranted. Citation Format: Shivani Soni, Yuji Miyamoto, Wu Zhang, Martin D. Berger, Shu Cao, Elizabeth Melendez, Alberto Puccini, Madiha Naseem, Ryuma Tokunaga, Francesca Battaglin, Michelle Mcskane, Chiara Cremolini, Alfredo Falcone, Fotios Loupakis, Heinz-Josef Lenz. Macrophage erythroblast attacher (MAEA) polymorphisms are associated with clinical outcome in TRIBE study mCRC patients treated with 5-fluorouracil/bevacizumab-based therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2614.