Abstract 4031: Distinct gene expression profile of recurrent stage II colorectal cancers in African American and Caucasian American patients.

Abstract

Abstract Objective: To determine gene expression profile of Stage II colorectal cancers (CRCs) based on disease recurrence and patient race/ethnicity. Background: About 25-35% of Stage II CRCs recur after potentially curative surgery. Furthermore, the incidence, recurrence, and mortality rates for CRC are higher in African Americans (AAs) relative to Caucasian Americans (CAs), even when they are diagnosed with early stage disease. Differences in tumor biology may contribute to this race-based disparity. Thus, identification of these ‘high-risk’ patients is an unmet medical need. Methods: Using GeneChip microarray technology, we obtained gene expression profiles for Stage II CRCs from 16 AA and 30 CA patients. Samples from recurrent disease, within 5 years post-surgery (n=5 in AA, n= 9 in CA) were compared against non-recurrent, within 10 years post-surgery, (n=11 in AA, and n=21 in CA) samples. The data were analyzed for expression differences at the gene level comparing AA with CA patients and further analyzed for functions and pathways. Results: In the samples of recurrent CRCs, a significant number of genes (n=561) were differentially expressed, with a false-discovery rate of ≤5%. Further analyses showed 253 genes differentially expressed within the AA recurrent subgroup and 317 genes in CA recurrent subgroup. In recurrent CRCs, there were 9 genes common to AA and CA patients, suggesting a common gene signature specific for Stage II disease. Canonical pathway analyses and interaction network analyses for these differentially expressed genes revealed that ERK/MAPK, protein kinase A, and CDK5 signaling were the top three affected signaling pathways in recurrent samples from AAs. In contrast, RhoA, integrin, and cell cycle control signaling were the top three affected pathways in Stage II CRCs of CAs. This suggests, for samples from CAs and AAs, a distinct race-based gene expression and downstream effects on pathways. Conclusion: A common gene expression signature, specific for stage II, together with a race-specific expression profile may have therapeutic implications for AA and CA patients. Citation Format: Trafina Jadhav, Dongquan Chen, Balananda-Dhurjati Kumar Putcha, Temesgen Samuel, James Posey, Martin Heslin, Upender Manne. Distinct gene expression profile of recurrent stage II colorectal cancers in African American and Caucasian American patients. [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 4031. doi:10.1158/1538-7445.AM2013-4031