Abstract C127: Lipocalin-2 links obesity-associated lipid stress to colorectal cancer health disparities in Hispanic patients
Abstract
Colorectal cancer (CRC) is the most prevalent gastrointestinal malignancy and the fourth most common cancer in the US. Additionally, it is the second leading cause of cancer-related mortality globally. Obesity and high-fat diets contribute to lipid metabolic reprogramming, a hallmark of CRC progression, yet the molecular mechanisms underlying obesity-associated CRC health disparities remain poorly understood. We hypothesized that lipocalin-2 (LCN2), a secreted glycoprotein involved in lipid transport and extracellular matrix remodeling, contributes to metabolic reprogramming in Hispanic CRC, through interactions with matrix remodeling proteins such as MMP9 and LOXL2. RNA sequencing was performed on CRC tissues and normal adjacent tissues (NATs) from Hispanic and non-Hispanic White (NHW) patients to identify differentially expressed genes (DEGs). Pathway enrichment analysis was conducted to identify dysregulated lipid metabolism pathways. Candidate lipid metabolism-associated genes (LCN2, SQLE, DHCR7, and PCSK9) identified through transcriptomic analysis were validated by quantitative RT-PCR and Western blotting, with LCN2 selected for further functional characterization. Lipid stress was induced using palmitic acid (PA) and oleic acid/palmitic acid (OA:PA) treatments. Cell viability was assessed using the CCK-8 assay, while LCN2 and MMP-9 protein expression were evaluated in whole-cell lysates and conditioned media. RNA sequencing of CRC and NATs from Hispanic and NHW patients identified 1,251 and 899 DEGs, respectively, of which 710 are Hispanic-specific and 358 NHW-specific DEGs, indicating distinct ethnicity-associated molecular signatures. Pathway analysis demonstrated enrichment of lipid metabolism pathways in Hispanic CRC. Selected lipid metabolism-associated genes (LCN2, SQLE, DHCR7, and PCSK9) were subsequently validated in Hispanic and NHW CRC tissue samples by qRT-PCR, confirming significant dysregulation of all four genes. Among these, LCN2 was prioritized for further investigation because of its multifaceted roles in lipid transport, inflammation and tumor progression, making it a promising biomarker of obesity-associated CRC. To explore its role, CRC cell lines were used to PA-induced lipid stress, which increased both intracellular and secreted LCN2 protein expression and was accompanied by elevated MMP9 protein levels. Our findings identify LCN2 as a potential biomarker of obesity-associated CRC health disparities. Future studies will employ Hispanic and NHW CRC patient-derived organoids to determine how lipid stress influences LCN2-mediated tumor growth, migration, and invasion in an ethnicity-specific context. Somrita Roy, Soumya Nair, Sourav Roy. Lipocalin-2 links obesity-associated lipid stress to colorectal cancer health disparities in Hispanic patients [abstract]. In: Proceedings of the 19th AACR Conference on the Science of Cancer Health Disparities; 2026 Oct 18-21; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2026;35(10 Suppl):Abstract nr C127.