Abstract 2374: Identifying ZNF469 as a biomarker in cancer of the colon and stomach
Authors: Aaron Shaykevich, Isaac Silverman, Radhashree Maitra
Journal: Cancer Research (2025)

Abstract Introduction: Zinc Finger Protein 469 (ZNF469) is a protein involved in the formation of the extracellular matrix. While the non-coding RNA linc-ZNF469-3 has previously been identified to be overexpressed in certain cancers and promote metastasis, there have yet to be any studies attempting to establish a link between the protein ZNF469 and cancer formation or growth. In this study, we attempt to determine whether ZNF469 may act as a biomarker in colon and stomach cancers. Methods: A systems biology approach was used to explore the impact of varying ZNF469 expression and mutations. Patient data was retrieved from the TCGA database. TIMER2.0 software was utilized for statistical analysis along with visualization. Results: The expression of ZNF469 was found to increase in cancer compared to non-tumor control in the colon (p = 2.4e-11) and stomach (p = 2.2e-17). Furthermore, Kaplan-Meier plots indicate that higher expression of ZNF469 resulted in worse probability of survival in colon (HR = 1.70, CI = 1.35-2.15) and stomach (HR =1.68, CI = 1.34-2.10). We also found an association between immune infiltration and ZNF469. In colon cancer, ZNF469 expression moderately correlated with the immune infiltration of macrophages (partial correlation = 0.50, p = 6.2e-27), neutrophils (partial correlation = 0.57, p = 3.9e-35), and dendritic cells (partial correlation = 0.56, p = 3.9e-34). In stomach cancer, these correlations were present but weaker in macrophages (partial correlation = 0.23, p = 6.5e-6), neutrophils (partial correlation = 0.25, p = 8.5e-7), and dendritic cells (partial correlation = 0.29, p = 1.6e-8). In the colon, arm level gain mutations of ZNF469 were found to correlate with altered immune infiltration in CD8+ T cells (p &amp;lt; 0.001), neutrophils (p &amp;lt; 0.001), and dendritic cells (p &amp;lt; 0.01) with a few additional mutations found to be significant as well. Conversely, in the stomach, arm level deletions were found to correlate with altered immune infiltration in B cells (p &amp;lt; 0.01), CD8+ T cells (p &amp;lt; 0.001), neutrophils (p &amp;lt; 0.05), and dendritic cells (p &amp;lt; 0.001) with additional mutations found to be significant. Conclusion: The increased expression of ZNF469 in stomach and colon cancer suggests that it may facilitate in oncogenesis and may be induced by rapid tumor growth. The expression correlating with worse outcomes further supports ZNF469 as a pro-oncogenic protein in these cancers. High ZNF469 levels were also correlated with higher immune infiltration, especially in colon cancer, and arm level gain or arm level deletion mutations were associated with altered immune infiltration. Overall, the findings suggest that ZNF469 can serve as a biomarker in colon and stomach cancers. ZNF469 is upregulated in these cancers, and the increase of ZNF469 correlates with both worse outcomes as well as increased immune infiltration. This data suggests that further research into ZNF469 may be beneficial in stomach and colon cancers. Citation Format: Aaron Shaykevich, Isaac Silverman, Radhashree Maitra. Identifying ZNF469 as a biomarker in cancer of the colon and stomach [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 2374.