Abstract 2400: Determinants of early recurrence in surgically-resected colon cancer: A multi-omics analysis

Abstract

Abstract Introduction: Colon cancer is the third most common cancer worldwide. The mainstay treatment for localized disease is surgical resection, often followed by adjuvant chemotherapy in stage III patients, and stage II patients with high-risk features. Unfortunately, some patients experience early local and/or distant recurrence. Besides classic anatomical/pathological tumor features, insight into the genomic determinants of early recurrence in colon cancer is lacking. Herein, we utilize a multi-omics approach to identify early-recurrence-specific features that could aid in more accurate risk stratification. Methods: We utilized the Cancer Genomic Atlas Colon Adenocarcinoma (TCGA-COAD) Database. Clinical, histopathological and genomic data were retrieved through the cBioPortal database. Our analysis was limited to patients with stage 2 or 3 (n = 390) disease based on the American Joint Committee on Cancer Code. Early recurrence (ER) was defined as disease relapse/recurrence within 12 months of sample acquisition post-surgery. Accordingly, patients were categorized into the ER and non-early recurrence (NER) groups based on a cut-off point of 12 months of disease-free survival. Results: The colon cancer ER and NER group included 45 and 345 patients, respectively. Comparable age, sex and race percentages were found between both groups. The ER group had significantly worse overall, progression-free, and disease-specific survival (HR: 0.083 95% CI: 0.031-0.220, HR: 0.035 95% CI: 0.011-0.0109, HR: 0.021 95% CI: 0.006-0.076, respectively). ER patients had a significantly higher proportion of patients with T4 and N2 disease based on the TNM staging system. ER patients had significant (P< 0.05) expression of TRIM46, TRPC4, ELOVL7, CSMD1, BCLAF1, and CD70 mutations, while tumor mutational burden was comparable between both groups (median TMB in ER vs NER: 4.2 vs 3.62, p = 0.28). Differential gene expression analysis revealed 68 genes to be upregulated in the ER group which were found to be enriched in hypoxia and interleukin-11 pathway genes. Genes upregulated in the NER group (n = 49) were enriched in interferon-alpha response and glycolysis/gluconeogenesis pathway genes. Proteomics analysis revealed significantly higher levels of EIF4E, CCNE1, SRSF1, SCD, and PECAM1 proteins in NER patients .Conclusion: Our results highlight insights into molecular and genomic features unique to colon cancer patients with early recurrence. Understanding such predictors for early recurrence will aid in risk stratification and help in determining patients who would derive the most benefit from adjuvant treatment considerations. Citation Format: Salma Al-Aomar, Hassan Abushukair, Alaa Zaitoun, Sara Zytoon, Sara Illeyyan, Husam Almomani, Ghayda'a Al-Majali, Arafat Hammad, Khaled Obeidat, Fuad Turfah, Awni Shahait, Fadwa Ali. Determinants of early recurrence in surgically-resected colon cancer: A multi-omics analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2400.