Abstract 4912: Assessing transcriptomic profiles of visceral adipose tissue in colon cancer patients
Authors: Patricia A. Erickson, Victoria M. Bandera, Bettina Katalin Budai, Tengda Lin, Caroline Himbert, Sheetal Hardikar, Jeffrey T. Yap, Elaine M. Glenny, Aik Choon Tan, Jennifer Ose, Christy A. Warby, Olena Aksonova, Tobias Nonnenmacher, Chris Stubben, David Nix, Kenneth Boucher, Peter Schirmacher, Ildiko Strehli, Alejandro Sanchez, Jolanta Jedrzkiewicz, Lyen C. Huang, Jessica N. Cohan, Alexander Brobeil, Hans-Ulrich Kauczor, Christoph Kahlert, Victoria Damerell, Erin M. Siegel, Doratha A. Byrd, Adetunji T. Toriola, David Shibata, Christopher I. Li, Jane C. Figueiredo, Jatin Roper, Biljana Gigic, Stephen Hursting, Cornelia M. Ulrich
Journal: Cancer Research (2025)

Background: Obesity is a major risk factor for colon cancer (CC) with a number of potential biologic mechanisms. Visceral adipose tissue (VAT) has been identified as a key contributor, partly due to its secretion of adipokines and proinflammatory cytokines. VAT has also been associated with worse cancer-related outcomes. In this study, we evaluated transcriptomic differences in patients with high versus low amounts of VAT among people with CC. Methods: Tumor-adjacent VAT was collected in 60 patients diagnosed with stage I-III CC who underwent primary surgery as part of the ColoCare Study at Huntsman Cancer Institute (HCI), University of Utah, and University of Heidelberg, Germany. Bulk transcriptomic analysis (RNAseq) was performed on VAT at the HCI genomics core. Computed tomography (CT) scans were used to measure visceral fat area (VFA) via body composition analysis performed using the Data Analysis Facilitation Suite (DAFS). The “DESeq2” R package was used to identify differentially expressed genes stratified by VFA (low VFA: &amp;lt;175 cm2, high VFA ≥ 175 cm2), adjusting for age at diagnosis, sex, study site, and tumor stage. Ranked/sorted genes were entered into gene set enrichment analysis (GSEA) software to identify enriched gene sets and pathways. Results: Among the 60 patients included the study, 53% were male, the mean age at diagnosis was 63±13 years, 45% had stage III CC, and the mean VFA was 182±105 cm2. Among patients with high VFA, 173 genes were differentially expressed compared to those with low VFA. GSEA identified 17 significantly upregulated and 20 significantly downregulated gene sets (p-adj. &amp;lt; 0.05). Upregulated gene sets among patients with high VFA included pathways were related to extracellular matrix signaling, pyrimidine metabolism, and cytokine-cytokine receptor interactions, while downregulated gene sets included pathways related to branched-chain amino-acid degradation, propanoate metabolism, and pyruvate metabolism. Discussion: VAT in patients with high levels of visceral adiposity was characterized by the overexpression of pathways that are thought to be associated with CRC development and progression. Our next steps involve further evaluation of these findings in a larger cohort, along with an assessment of VAT gene expression in relation to survival. Citation Format: Patricia A. Erickson, Victoria M. Bandera, Bettina Katalin Budai, Tengda Lin, Caroline Himbert, Sheetal Hardikar, Jeffrey T. Yap, Elaine M. Glenny, Aik Choon Tan, Jennifer Ose, Christy A. Warby, Olena Aksonova, Tobias Nonnenmacher, Chris Stubben, David Nix, Kenneth Boucher, Peter Schirmacher, Ildiko Strehli, Alejandro Sanchez, Jolanta Jedrzkiewicz, Lyen C. Huang, Jessica N. Cohan, Alexander Brobeil, Hans-Ulrich Kauczor, Christoph Kahlert, Victoria Damerell, Erin M. Siegel, Doratha A. Byrd, Adetunji T. Toriola, David Shibata, Christopher I. Li, Jane C. Figueiredo, Jatin Roper, Biljana Gigic, Stephen Hursting, Cornelia M. Ulrich. Assessing transcriptomic profiles of visceral adipose tissue in colon cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4912.