Correlation of GI cancer antigens expression or association with patient survival outcomes using TCGA data

Background: Cancers of the GI system, including the esophagus, stomach, colon, rectum, pancreas, liver, and biliary tract, comprise a significant portion of the global cancer burden. Recently, tumor-associated antigens (TAAs) have been shown to be useful in targeted cancer therapies and as markers. Although many GI cancer-related TAAs have been identified, treatments could be improved if they could target multiple antigen profiles simultaneously. This study first examines the expression of eight well-known GI cancer-specific TAAs: MMP7, TACSTD2, FOLR1, EPCAM, AADAT, MSLN, CLDN18, and CEACAM5; then it investigates their relationships with each other and with patient survival. Methods: The Cancer Genome Atlas (TCGA) database; UALCAN was used to analyze the expression profile of TAA in normal and tumor samples, along with their significance. The effects of each TAA on survivability (Kaplan-Meier) and their significance were also analyzed. Survival plots and significance were calculated using log-rank tests. Lastly, Pearson correlations between the eight antigens across all seven cancers were obtained from the Gene Expression Profiling Interactive Analysis (GEPIA) portal. Results: Across GI cancers show that TAA expression varies from that in normal tissue. MMP7 and MSLN are the most commonly upregulated. Most cancers exhibit three or more antigens that are increased, except for LIHC, where MMP7, EPCAM, and AADAT are downregulated. Only five of eight TAAs correlate with survival: EPCAM and MMP7 in STAD, FOLR1 and CLDN18 in LIHC, EPCAM in ESCA, and MSLN in PAAD. Correlations are mostly weak to moderate, except TACSTD2, which is negatively correlated with all ESCA antigens. Conclusion: Since MMP7 and MSLN are broadly upregulated in GI cancers, these TAAs could be studied further as potential targets for pan-GI therapies. Cancers with multiple high-impact upregulations associated with survival may be suitable for treatment with multi-antigen antibody or CAR-T therapies, such as EPCAM and MMP7 for STAD. Additionally, the weak correlations among the TAAs suggest that somewhat independent mechanisms might regulate their expression. Therefore, this implies that therapies targeting a single antigen may not be fully effective.