S453 Characterization of Survival Outcomes for Differentially Expressed COL5A1, COL5A2, and COL1A1 in Gastrointestinal Cancers

Introduction: Collectively, gastrointestinal (GI) cancers account for approximately 26% of all cancer diagnoses and over 35% of all cancer-related deaths worldwide. The genes COL5A1, COL5A2, and COL1A1 have been shown to contribute to proliferation and migration of tumor cells. Methods: The Cancer Genome Atlas Colon Adenocarcinoma, STAD, READ, and ESCA project clinical data and STAR counts for the COL5A1, COL5A2, and COL1A1 genes were queried. 3,720 patients were separated into high expression or low expression groups based on median expression levels. Kaplan-Meier survival curves were generated to compare survival between groups based on primary cancer site. These curves were regenerated after regrouping primary sites into colorectal, esophagus, and stomach to achieve higher n values. Univariate and multivariate Cox Proportional Hazards Models were created for the groups assessing American Joint Committee on Cancer pathologic stage, M, N, and T, ethnicity, gender, race, primary site, and primary diagnosis. Results: The high expression group (HEG) had significantly worse survival than the low expression group (LEG) (P = 0.039). Primary colon (high (H) vs comparison (C) P = 3.66e-06, low (L) vs C P = 0.00068) and stomach cancers (H vs C P = 6.47e-06, L vs C P = 0.0125) were significant. After grouping, colorectal (H vs C P = 3.93e-06, L vs C P = 0.000207) and stomach cancers (H vs C P = 0.00153, L vs C P = 0.0333) were significant. In multivariate COX analysis, HEG had significantly worse mortality for M1 (hazard ratio [HR] 3.40, P = 0.001), M1a (HR 9.79, P < 0.001), M1b (HR 9.31, P < 0.001), N2a (HR 3.25, P = 0.033), cardia (HR 2.16, P = 0.022), stomach (HR 12.5, P < 0.001), thoracic esophagus (HR 7.35, P = 0.025), and transverse colon (HR 4.36, P = 0.048). LEG had significantly worse mortality for M1 (HR 8.66, P < 0.001), M1a (HR 5.85, P = 0.036), M1b (HR 16.2, P = 0.002), cardia (HR 1.93, P = 0.052), stomach (HR 6.42, P = 0.017), thoracic esophagus (HR 17.0, P < 0.001), transverse colon (HR 10.1, P = 0.003), esophagus (HR 35.6, P = 0.021), and papillary adenocarcinoma (HR 17.3, P = 0.019). Conclusion: Differential expression of these genes in GI cancer leads to significant differences in survival and could serve as prognostic markers or therapeutic targets. Low expression in early metastasis and in thoracic esophagus, transverse colon, and stomach cancer may play a role in disease progression. Primary colon and stomach cancers are the most significantly impacted by differential expression which may be explained by their high collagen RNA expression compared to other GI sites.