Abstract LB251: Widespread epigenetic deregulation and its dependency on tumor sidedness in colorectal cancer

Abstract

Abstract Clinical evidence suggests that right-sided colorectal cancer (CRC) tends to have a worse prognosis compared to left-sided CRC. The distinct functional mechanisms underlying this “sidedness” remain cryptic and poorly understood. Thus, molecular classification of CRC is of paramount in targeting specific subtypes and personalizing treatment for patients. To identify targetable molecular features to improve treatment regimens, we performed multi-faceted network analyses of a large number of CRC patients. In our network model, differential expression of transcript abundance, epigenetic features, and mutational frequency were used to identify widespread gene dysregulation and perturbed pathways to reveal disrupted networks distinct to right or left sided colorectal cancer. We discovered histone related genes and distinct epigenetic signals are at play in right-sided CRC. Additionally, our studies reveal “at risk” patient characteristics suggestive of survival differences, to improve diagnostic predictors based on CRC sidedness. Overall, our integrative approach serves to link molecular profiles distinct between left and right sided colorectal cancer, while paving the way towards identifying more effective treatment alternatives from a previously overlooked, readily characterized subtype of colorectal cancer. Citation Format: Brandon Burgman, Xingxin Pan, Anjali Agrawal, Nidhi Sahni, S. Stephen Yi. Widespread epigenetic deregulation and its dependency on tumor sidedness in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB251.