Abstract 6311: Clinical assessment of DPEP1 expression and its interacting genes in tumor (T) and adjacent normal tissue (NAT) of colorectal cancer

Abstract Colorectal cancer (CRC) is one of the deadliest cancers worldwide with an estimated global rise of 60% cases by 2030. Over the last decade, advances in surgical-, chemo-, targeted-, and immuno- therapies have significantly improved survival rates, but novel biomarkers are required for the design of better screening and therapeutic strategies for CRC patients. The tumor (T) and adjacent normal tissue (NAT) can capture tumor heterogeneity and assist in the molecular classification of the tumors. In this study, we explored the clinical and molecular features of Dipeptidase (DPEP1)-related gene expression in CRC. DPEP1 is an enzyme involved in the conversion of leukotrienes and functions as an adhesive receptor for neutrophil recruitment in inflamed tissue. Primary analysis using the TCGA (The Cancer Genome Atlas) dataset identified survival and tumorigenic role of DPEP1-related gene network in COAD (colon adenocarcinoma) dataset. Higher expression of DPEP1-interacting genes (KIF1BP, GGT5, GGT1, DPEP2, and DPEP3) was found to be associated with worse overall and progression-free survival (log-rank p-value <0.01). To further characterize the distribution of the DPEP1 as a hub gene, we quantified its expression in the Augusta University cohort (40 patients, 80 T/NAT pairs). FFPE (Formalin-fixed paraffin-embedded) blocks were sectioned to extract tissue sections and were subsequently stained using H&E (Hematoxylin and eosin dyes) to identify the tumor and normal regions. Total RNA was isolated from the tumor-rich and adjacent normal regions separately post macrodissection. The mRNA molecules were quantified using a medium throughput NanoString platform. The expression of DPEP1 was found to be significantly higher (2.5-fold) in tumor-rich regions compared to adjacent normal. A similar trend of higher expression in tumors was observed in the orthologous TCGA-COAD dataset. Immune cell infiltration analysis identified a positive correlation between DPEP1 expression and M2 macrophages (p-value <0.01). Generally, the M2 subtype of macrophages has been known to exhibit immunosuppressive and pro-tumor properties. Additional gene set enrichment analysis identified an inverse association between DPEP1 expression and the Interferon-gamma signaling pathway (NES = -2.4, p-value <0.01). In conclusion, higher expression of DPEP1-related gene expression has a prognostic influence on CRC. Its positive association with M2 macrophages and negative association with anti-tumor cytokines forms a distinct subtype of CRC tumor that can benefit from emerging immunotherapies. Citation Format: Pankaj Ahluwalia, Ashis K. Mondal, Kimya Jones, Ravindra Kolhe. Clinical assessment of DPEP1 expression and its interacting genes in tumor (T) and adjacent normal tissue (NAT) of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6311.