Abstract 2439: Potential target genes for early stage detection in Hispanic colorectal cancer
Authors: Caraballo Elba V. , Zenón-Meléndez Camille , Pérez-Santiago Josué , Cruz-Correa Marcia 
Published: March 2024

Background: Colorectal Cancer (CRC) has become the second leading cause of death related to cancer worldwide and the third most common malignancy. CRC tumors are classified into stages to describe the cancer; early (stages I and II) and advanced (stages III and IV). Despite the available screening methods and the scientific efforts in the development of a universal biomarker panel for CRC early detection, there still exists a gap in a reliable non-invasive screening method for the Hispanic community. We aimed to elucidate the most important pathways along with the differential gene expression in early and advanced CRC stages in a Hispanic population.

Methods: We examined restrospectively 7 tissue samples from a Puerto Rican Hispanic population recruited throughout the Puerto Rico Familial Colorectal Cancer Registry (PURIFICAR) IRB #A2210207. We evaluated transcriptomic changes in advance tumors (n=4) vs. early tumors (n=3) with their respective normal mucosal tissue as negative control. Extracted RNA was sequenced using the Illumina NextSeq (2 × 75bp). The higher-quality reads were aligned, annotated, and quantified to the human genome (hg38) using STAR and RSEM softwares. Gene expression analysis was performed in R statistical software (packages tximport and DESeq2). We compared significantly expressed genes (adjusted p-value &lt;0.05) between study groups (Tumor Advance [TA] vs. Mucosal Advance [MA] and Tumor Early [TE] vs. Mucosal Early [ME]) using Venny, and we performed enrichment analyses and protein-protein interaction networks using Metascape and STRING database, respectively.

Results: There were 2284 differentially expressed genes (TA vs. MA) and 984 (TE vs. ME), in which 1736 were unique to advance stages, 436 were unique to early stages and 548 were shared in both tumor stages. Significantly impacted biological processes and pathways include: granulocyte chemotaxis, regulation of inflammatory response, positive regulation of apoptotic process, tissue morphogenesis, G alpha signaling events, interleukin-10 signaling, signaling by interleukins. Additionally, physical and functional interaction networks showed 11 major clusters (≥ 5 genes), which contained several gene hubs including LYN (proto-oncogene), IL-1β, IL-1α, TNF, CCL3, CCL4, CXCR1 and CXCR2 (cytokines/chemokines) among others genes previously reported as CRC biomarkers (DKK1, AQP8, AQP9, CTNNB1, and GNAQ).

Discussion/Conclusions: Differential analysis of early CRC tumor samples shows a deregulation of genes related to the inflammatory response which plays an important role in CRC. Modulation of these genes suggests significant potential targets for early detection of CRC in a Hispanic population. Future studies will be focus on the evaluation of selected target genes as a non-invasive early CRC screening method.

Citation Format: Elba V. Caraballo, Camille Zenón-Meléndez, Josué Pérez-Santiago, Marcia Cruz-Correa. Potential target genes for early stage detection in Hispanic colorectal cancer [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 2439.