Abstract 2330: The Jekyll and Hyde of DARC: Balancing prognosis and metastasis in breast cancer

Abstract Background: DARC, a decoy receptor for chemokines, is implicated in breast cancer progression. Understanding its interplay with key molecular markers and its impact on tumor behaviour is crucial for developing targeted therapies. Methodology: This study employed a multi-faceted approach, including immunohistochemistry, quantitative PCR, and bioinformatical analysis of publicly available datasets (TCGA and METABRIC). The DARC, CCL8, c-MYC, ALDH1, and CHEK2 expression patterns were analyzed in breast cancer tissues. Correlation analyses and survival analyses were performed to assess the prognostic significance of these markers. Results: Our findings revealed a positive correlation between DARC and CCL8 expression, suggesting a potential role of DARC in promoting tumor cell migration and invasion through CCL8 signalling. Additionally, elevated DARC expression was associated with increased c-MYC, ALDH1, and CHEK2 levels, indicating its potential involvement in tumor cell proliferation, stemness, and chemoresistance. Bioinformatical analysis further corroborated these findings and identified DARC as a potential prognostic biomarker. Conclusion: These results highlight the complex interplay between DARC and key molecular markers in breast cancer. Targeting DARC may offer a novel therapeutic strategy to inhibit tumor progression and improve patient outcomes. Further validation studies are warranted to elucidate the precise mechanisms underlying DARC-mediated tumorigenesis. Citation Format: Joyeeta Talukdar, Trayambak Srivastava, Ruby Dhar, Subhradip Karmakar. The Jekyll and Hyde of DARC: Balancing prognosis and metastasis in breast cancer [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 2330.