Tissue- and cell-type–specific genetic regulation of CTBP1 in breast cancer: A comprehensive review
Breast cancer remains a significant global health challenge, with rising incidence and mortality rates posing a critical public health concern. Despite advancements in early diagnosis and treatment, clinical outcomes remain unpredictable due to tumor heterogeneity, treatment resistance, and immune evasion mechanisms. This underscores the urgent need for novel biomarkers to predict risk, assess prognosis, and guide personalized therapeutic strategies.
Metabolic reprogramming is emerging as a key hallmark of cancer initiation and progression. Among post-translational modifications, lysine succinylation has gained attention as a regulator of tumor biology. This modification influences protein structure, function, gene expression, metabolic flux, and immune signaling.
While the role of succinylation in tumor biology is recognized, its specific mechanisms in breast cancer, particularly in the immune microenvironment and imaging characteristics, remain under-explored. This knowledge gap hinders the development of targeted interventions and prognostic tools. Therefore, integrating metabolic information, immune response, and imaging features based on succinylation is crucial for developing comprehensive breast cancer prognostic models.
CTBP1, a transcriptional corepressor, has been implicated in cancer biology, promoting tumor proliferation, epithelial-mesenchymal transition (EMT), and metastasis through various pathways. In breast cancer, CTBP1 interacts with metabolic and chromatin modifiers, linking redox homeostasis to oncogenic transcriptional programs. This study aimed to prioritize CTBP1 in breast cancer by integrating tissue-relevant genetic instruments with disease GWAS and exploring cell-type–specific signals. Expression, survival, and radiomics correlations were used to generate hypothesis-generating evidence.
CTBP1's role in breast cancer is multifaceted. It bridges cellular metabolism with transcriptional control and immune regulation. Prior studies have shown that CTBP1 represses E-cadherin and modulates redox-sensitive transcription factors, influencing tumor invasiveness and immune evasion. However, its regulation appears context-dependent and may differ across tissue or cell types.
To address these gaps, the study integrates genetic, single-cell, and MRI radiomics data to characterize CTBP1 regulation across multiple biological levels. The materials and methods section outlines the selection of hotspot genes, eQTL dataset, breast cancer outcome dataset, two-sample MR framework, SMR framework, differential expression analysis, survival analysis, single-cell MR analysis, DCE-MRI radiomics correlation, and single-cell capture and library preparation.
The results section presents the causal relationship between CTBP1 and breast cancer, potential prognostic and expression patterns, sceQTL analysis with CTBP1, radiomics correlations with CTBP1, and the immune microenvironment of BRCA. The discussion section highlights the context-dependent role of CTBP1 in breast cancer, its associations with systemic and cell-type-specific levels, and the implications for further study.
In conclusion, the study's comprehensive approach provides valuable insights into CTBP1's role in breast cancer, emphasizing the need for further research to clarify biological pathways and its potential translational relevance.
