Abstract 2353: CRHBP, a novel multiple cancer biomarker connected with better prognosis and anti-tumorigenicity

Abstract Corticotropin-releasing hormone-binding protein (CRHBP) is a key modulator of the hypothalamic-pituitary-adrenal (HPA) axis and plays a crucial role in stress responses, immune regulation, and neuroendocrine functions. Despite its importance in physiological processes, the role of CRHBP in tumor biology and its clinical relevance remain largely unknown. This study aims to comprehensively investigate CRHBP expression across diverse cancer types, its prognostic significance, and its potential molecular mechanisms in tumor progression. We show that CRHBP expression was consistently downregulated in the majority of solid tumors, with the most significant reductions observed in LUAD, LIHC, and KIRC. Low CRHBP expression was strongly correlated with poor prognosis, including shorter OS and DFS, in multiple tumor types. Methylation analysis revealed that hypermethylation of the CRHBP promoter region was associated with its downregulation in several cancers. Further, we identified a set of miRNAs (miR-21, miR-155, miR-29a, and miR-181a) that were upregulated in these tumors and may contribute to the suppression of CRHBP expression. Gene enrichment analysis revealed that CRHBP is involved in key cellular processes, including intracellular signal transduction, metabolic regulation, and hormone-related pathways. CRHBP expression also showed significant correlations with the immune microenvironment, particularly with the infiltration of regulatory T cells (Tregs), macrophages, and dendritic cells. PPI network analysis indicated that CRHBP interacts with several proteins involved in the stress response, immune regulation, and cellular metabolism. Functionally, overexpression of CRHBP inhibited tumor cell proliferation in LUAD, LIHC, and KIRC cell lines, as measured by MTT and colony formation assays. Furthermore, CRHBP overexpression significantly reduced cell migration and invasion in KIRC and hepatocellular carcinoma (HCC) cell lines. Together, these data demonstrated that CRHBP expression is associated with tumor progression, immune cell infiltration, and key molecular pathways. Overexpression of CRHBP inhibits cell proliferation and mobility in multiple cancers, suggesting its potential as a biomarker and therapeutic target in cancer. Citation Format: Wonbeak Yoo, Yeeun Lee, Kyung Chan Park, Hyunji Choi. CRHBP, a novel multiple cancer biomarker connected with better prognosis and anti-tumorigenicity [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 2353.