Tissue- and Cell-Type-Specific Genetic Regulation of CTBP1 in Breast Cancer: Integrative Analyses with Exploratory Single-Cell and Imaging Data.

Background: CTBP1, an NADH-dependent transcriptional co-repressor subject to succinylation, may orchestrate both systemic and cell-type-specific effects on tumor development. Methods: This integrative study represents a novel approach, combining genetic regulation, single-cell expression quantitative trait loci (eQTLs), and imaging radiomics to investigate CTBP1 in breast cancer. We integrated tissue-relevant eQTLs with breast cancer GWAS to evaluate genetically proxied associations for CTBP1. We further explored cell-type-dependent effects using single-cell eQTL resources and examined expression, survival, and imaging correlations as hypothesis-generating evidence. Results: Tissue-focused analyses suggested an inverse association between CTBP1 expression and breast cancer risk, with consistent directions observed in expression and survival datasets. Single-cell explorations indicated potential cell-type-specific regulation.Imaging correlations with MRI-derived features were modest and exploratory. Conclusion: Our results prioritise CTBP1 as a context-dependent, tissue- and cell-type-specific candidate in breast cancer. The observational and exploratory components warrant validation in larger cohorts and functional assays. To our knowledge, this is the first integrative study combining GWAS, single-cell eQTL and MRI radiomics to prioritize CTBP1 in breast cancer.