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

Area of Science:

• Oncology
• Genetics
• Bioinformatics

Background:

• CTBP1 (C-terminal binding protein 1) is an NADH-dependent transcriptional co-repressor.
• CTBP1 is subject to succinylation, influencing its function.
• CTBP1 may play a role in both systemic and cell-type-specific tumor development.

Purpose of the Study:

• To investigate the role of CTBP1 in breast cancer using an integrative approach.
• To evaluate genetically proxied associations for CTBP1 in breast cancer.
• To explore cell-type-dependent effects and correlations with imaging features.

Main Methods:

• Integration of genetic regulation, single-cell expression quantitative trait loci (eQTLs), and imaging radiomics.
• Analysis of tissue-relevant eQTLs integrated with breast cancer Genome-Wide Association Studies (GWAS).
• Examination of CTBP1 expression, survival data, and MRI-derived radiomic features.

Main Results:

• Tissue-focused analyses indicated an inverse association between CTBP1 expression and breast cancer risk.
• Consistent directions were observed between CTBP1 expression and survival datasets.
• Single-cell analyses suggested potential cell-type-specific regulation of CTBP1; imaging correlations were modest.

Conclusions:

• CTBP1 is prioritized as a context-dependent, tissue- and cell-type-specific candidate in breast cancer.
• The study's observational and exploratory findings require validation in larger cohorts and functional assays.
• This is the first integrative study combining GWAS, single-cell eQTL, and MRI radiomics to prioritize CTBP1 in breast cancer.