Abstract 1024: Differential gene expression of colorectal cancer biomarkers in Hispanic individuals
Cancer Research(2024)
Abstract
Abstract Colorectal cancer (CRC) is a leading cause of cancer death among men and women in Puerto Rico and the United States. About 60-70% of CRC cases are found at advanced stages (III/IV), suggesting limited adherence to available screening methods. Several molecular biomarkers have been identified as discriminatory for CRC (e.g., KRAS, NRAS, MSI), improving CRC management and patient outcomes. This study evaluates the differential expression patterns of DKK3, PKM2, IGFBP2, and SEPT9 genes between matched CRC tumors and adjacent mucosa samples. The secondary outcome was to examine the association between the presence of the selected biomarkers in tissue compared to blood samples. Using a retrospective study design, we examined 112 tissue samples of Hispanic individuals with a pathology-confirmed CRC diagnosis recruited throughout the Puerto Rico Familial Colorectal Cancer Registry (PURIFICAR). We quantified expression levels of target genes by RT-qPCR normalized with endogenous control GAPDH, using TaqMan Gene Expression Assay in the QuantStudio 3 (Applied Biosystems). Wilcoxon signed-rank test was used to calculate differences between gene expression from tumor and adjacent mucosal tissue samples. Additionally, 39 paired blood and tissue samples were analyzed to explore the association between biomarkers in these two types of samples. Protein biomarkers were measured using a commercially available ELISA kit according to manufacturer protocols (Thermo Scientific Federick, MD and Biosource San Diego, CA). mSEPT9 was measured using the Epi proColon® 2.0 CE test. The association between biomarker presence in tissue and blood samples was assessed using the Chi-square test of independence, with biomarker concentrations dichotomized at the median value. Statistical analyses were performed using Stata 17 and R version 4.3.1. DKK3 and IGFBP2 expression levels were higher among CRC tumor samples. However, expression levels of PKM2 and SEPT9 genes were slightly lower. DKK3 was the only target gene significantly different (p<0.05) when comparing overall gene expression between the matched samples. Upon comparison between early and advanced CRC stages, DKK3 expression levels were higher in advanced-stage tumor samples when compared to adjacent mucosal tissue samples (p<0.05). Moreover, a significant association between IGFBG2 presence in tissue compared to blood was detected at a 90% confidence level (p-value<0.10). This association was evident in early-stage CRC cases; there is a relationship between IGFBG2 biomarker presence in tissue and IGFBG2 biomarker presence in blood (p<0.05). Our findings indicate DKK3 and IGFBP2 as potential biomarkers for CRC progression and early detection. The study’s insights into the differential expression patterns of these biomarkers can inform targeted screening strategies. Further research is needed to assess their potential to enhance early tumor detection in Hispanics. Citation Format: Elba V. Caraballo-Rivera, Hilmaris Centeno-Girona, Gabriel De Jesus-Astacio, Camille Zenon-Melendez, Brenda Torres-Velasquez, Madeline Martir-Ocasio, Marcia R. Cruz-Correa. Differential gene expression of colorectal cancer biomarkers in Hispanic individuals [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 1024.
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