CTBP1: A Key Regulator Linking Metabolism, Immunity, and Imaging in Breast Cancer – A Comprehensive Analysis

Breast cancer continues to be a leading cause of cancer-related deaths among women worldwide, presenting a ample global health challenge. Despite advances in detection and treatment, unpredictable clinical outcomes persist due to the inherent complexity of the disease, characterized by tumor heterogeneity, the progress of treatment resistance, and sophisticated immune evasion mechanisms.Consequently, identifying novel and reliable biomarkers for accurate risk prediction, robust prognostic assessment, and the development of personalized therapeutic strategies is of paramount importance.

Emerging research highlights metabolic reprogramming as a basic hallmark of cancer initiation and progression. Within the landscape of post-translational modifications (PTMs) that govern cancer metabolism and immune surveillance, lysine succinylation has gained prominence as a critical regulator of tumor biology. This modification alters protein structure and function, influencing gene expression, metabolic pathways, and immune signaling cascades.

While the role of succinylation in cancer is increasingly recognized,its specific mechanisms within breast cancer remain largely unexplored,especially concerning its interplay with the immune microenvironment and imaging characteristics.This knowledge gap hinders the development of targeted therapies and effective prognostic tools. Therefore, a comprehensive prognostic model integrating metabolic data, immune responses, and imaging features, centered around succinylation, holds notable clinical promise.

This need is further underscored by the multifaceted role of C-terminal Binding Protein 1 (CTBP1). Extensively studied in cancer biology,CTBP1 functions as a transcriptional corepressor,promoting tumor proliferation,epithelial-mesenchymal transition (EMT),and metastasis through pathways such as the CDH1 repression axis and TGF-β signaling. Moreover, CTBP1 interacts with metabolic and chromatin modifiers, establishing a crucial link between redox homeostasis and oncogenic transcriptional programs in both breast cancer and othre malignancies. these findings strongly support the investigation of tissue- and cell-specific regulatory mechanisms of CTBP1 in the context of breast cancer.

This study prioritized CTBP1 in breast cancer by integrating tissue-relevant genetic instruments with genome-wide association study (GWAS) data and exploring cell-type-specific signals. The research was complemented by correlations between gene expression,patient survival data,and magnetic resonance imaging (MRI) radiomics,serving as hypothesis-generating evidence for potential biomarkers. CTBP1 is particularly compelling due to its ability to bridge cellular metabolism with transcriptional control and immune regulation. Previous research has demonstrated CTBP1’s role in repressing E-cadherin and modulating redox-sensitive transcription factors, impacting tumor invasiveness and immune evasion. However, its regulation appears to be context-dependent, varying across tissues and cell types. To address these complexities, this study integrates genetic, single-cell, and MRI radiomics data to systematically characterize CTBP1 regulation across multiple biological levels.

Materials and Methods

Selection of Hotspot Genes:

A total of 19 succinylation-related genes were selected for this study, based on prior research.A comprehensive list of these genes is available in supplemental Table S1. The overall study workflow is summarized in Supplementary Figure S1.

**eQ

CTBP1: A Key Regulator Linking Metabolism, Immunity, and Imaging in Breast Cancer – A Comprehensive Analysis

Breast cancer continues to be a leading cause of cancer-related deaths among women worldwide, presenting a substantial global health challenge. Despite advances in detection and treatment, unpredictable clinical outcomes persist due to the inherent complexity of the disease, characterized by tumor heterogeneity, the development of treatment resistance, and sophisticated immune evasion mechanisms. Consequently, identifying novel and reliable biomarkers for accurate risk prediction, robust prognostic assessment, and the development of personalized therapeutic strategies is of paramount importance.

Emerging research highlights metabolic reprogramming as a fundamental hallmark of cancer initiation and progression. Within the landscape of post-translational modifications (PTMs) that govern cancer metabolism and immune surveillance, lysine succinylation has gained prominence as a critical regulator of tumor biology.This modification alters protein structure and function, influencing gene expression, metabolic pathways, and immune signaling cascades.

While the role of succinylation in cancer is increasingly recognized, its specific mechanisms within breast cancer remain largely unexplored, particularly concerning its interplay with the immune microenvironment and imaging characteristics. this knowledge gap hinders the development of targeted therapies and effective prognostic tools. Thus,a comprehensive prognostic model integrating metabolic information,immune responses,and imaging features,centered around succinylation,holds significant clinical promise.

This need is further underscored by the multifaceted role of C-terminal Binding Protein 1 (CTBP1). Extensively studied in cancer biology, CTBP1 functions as a transcriptional corepressor, promoting tumor proliferation, epithelial-mesenchymal transition (EMT), and metastasis through pathways such as the CDH1 repression axis and TGF-β signaling. Furthermore, CTBP1 interacts with metabolic and chromatin modifiers, establishing a crucial link between redox homeostasis and oncogenic transcriptional programs in both breast cancer and other malignancies. These findings strongly support the investigation of tissue- and cell-specific regulatory mechanisms of CTBP1 in the context of breast cancer.

This study prioritized CTBP1 in breast cancer by integrating tissue-relevant genetic instruments with genome-wide association study (GWAS) data and exploring cell-type-specific signals. The research was complemented by correlations between gene expression, patient survival data, and magnetic resonance imaging (MRI) radiomics, serving as hypothesis-generating evidence to identify potential biomarkers. CTBP1 is of particular interest due to its ability to bridge cellular metabolism with transcriptional control and immune regulation. previous research has demonstrated CTBP1’s role in repressing E-cadherin and modulating redox-sensitive transcription factors, impacting tumor invasiveness and immune evasion. However, its regulation is context-dependent and likely varies across diffrent tissues and cell types. To address these complexities, this study integrates genetic, single-cell, and MRI radiomics data to systematically characterize CTBP1 regulation across multiple biological levels.

Materials and Methods

Selection of Hotspot Genes:

A total of 19 succinylation-related genes were selected for this study, as detailed in Supplemental Table S1. The overall workflow is summarized in Supplementary Figure S1.

eQTL Dataset:

Expression quantitative trait loci (eQTL) data for the selected genes were obtained from the

CTBP1: A Key Regulator Linking Metabolism,Immunity,and Imaging in Breast Cancer – A Comprehensive Analysis

Breast cancer continues to be a leading cause of cancer-related deaths among women worldwide,presenting a substantial global health challenge.Despite advances in detection and treatment, unpredictable clinical outcomes persist due to the inherent complexity of the disease, characterized by tumor heterogeneity, the development of treatment resistance, and sophisticated immune evasion mechanisms. Consequently, identifying novel and reliable biomarkers for accurate risk prediction, robust prognostic assessment, and the development of personalized therapeutic strategies is of paramount importance.

Emerging research highlights metabolic reprogramming as a fundamental hallmark of cancer initiation and progression. within the landscape of post-translational modifications (PTMs) that govern cancer metabolism and immune surveillance, lysine succinylation has gained prominence as a critical regulator of tumor biology. This modification alters protein structure and function, influencing gene expression, metabolic pathways, and immune signaling cascades.

While the role of succinylation in cancer is increasingly recognized, its specific mechanisms within breast cancer remain largely unexplored, particularly concerning its interplay with the immune microenvironment and imaging characteristics. This knowledge gap hinders the development of targeted therapies and effective prognostic tools. Therefore, a comprehensive prognostic model integrating metabolic information, immune responses, and imaging features, centered around succinylation, holds significant clinical promise.

This need is further underscored by the multifaceted role of C-terminal Binding Protein 1 (CTBP1).Extensively studied in cancer biology, CTBP1 functions as a transcriptional corepressor, promoting tumor proliferation, epithelial-mesenchymal transition (EMT), and metastasis through pathways such as the CDH1 repression axis and TGF-β signaling. Furthermore, CTBP1 interacts with metabolic and chromatin modifiers, establishing a crucial link between redox homeostasis and oncogenic transcriptional programs in both breast cancer and other malignancies. These findings strongly support the investigation of tissue- and cell-specific regulatory mechanisms of CTBP1 in the context of breast cancer.

This study prioritized CTBP1 in breast cancer by integrating tissue-relevant genetic instruments with genome-wide association study (GWAS) data and exploring cell-type-specific signals. The research was complemented by correlations between gene expression, patient survival data, and magnetic resonance imaging (MRI) radiomics, serving as hypothesis-generating evidence to identify potential biomarkers. CTBP1 is of particular interest due to its ability to bridge cellular metabolism with transcriptional control and immune regulation. Previous research has demonstrated CTBP1’s role in repressing E-cadherin and modulating redox-sensitive transcription factors, impacting tumor invasiveness and immune evasion.Though, its regulation appears to be context-dependent and may vary across different tissues or cell types. To address these complexities, this study integrates genetic, single-cell, and MRI radiomics data to systematically characterize CTBP1 regulation across multiple biological levels.

Materials and Methods

selection of Hotspot Genes:

A total of 19 succinylation-related genes were selected for this study, as detailed in Supplemental Table S1. The overall workflow is summarized in Supplementary Figure S1.

eQTL Dataset:

Expression quantitative trait loci (eQTL) data for the selected genes were obtained from the eQTLGen database ([https://wwweqtlgen[https://wwweqtlgen

CTBP1: A Key Regulator Linking Metabolism, Immunity, and Imaging in Breast Cancer – A Comprehensive Analysis

Breast cancer continues to be a leading cause of cancer-related deaths among women worldwide, presenting a substantial global health challenge. Despite advances in detection and treatment, unpredictable clinical outcomes persist due to the inherent complexity of the disease, characterized by tumor heterogeneity, the development of treatment resistance, and sophisticated immune evasion mechanisms. consequently, identifying novel and reliable biomarkers for accurate risk prediction, robust prognostic assessment, and the development of personalized therapeutic strategies is of paramount importance.

Emerging research highlights metabolic reprogramming as a fundamental hallmark of cancer initiation and progression. Within the landscape of post-translational modifications (PTMs) that govern cancer metabolism and immune surveillance, lysine succinylation has gained prominence as a critical regulator of tumor biology. This modification alters protein structure and function, influencing gene expression, metabolic pathways, and immune signaling cascades.

While the role of succinylation in cancer is increasingly recognized, its specific mechanisms within breast cancer remain largely unexplored, particularly concerning its interplay with the immune microenvironment and imaging characteristics. This knowledge gap hinders the development of targeted therapies and effective prognostic tools. Thus, a comprehensive prognostic model integrating metabolic information, immune responses, and imaging features, centered around succinylation, holds significant clinical promise.

this need is further underscored by the multifaceted role of C-terminal Binding Protein 1 (CTBP1). Extensively studied in cancer biology, CTBP1 functions as a transcriptional corepressor, promoting tumor proliferation, epithelial-mesenchymal transition (EMT), and metastasis through pathways such as the CDH1 repression axis and TGF-β signaling. Furthermore, CTBP1 interacts with metabolic and chromatin modifiers, establishing a crucial link between redox homeostasis and oncogenic transcriptional programs in both breast cancer and other malignancies. These findings strongly support the investigation of tissue- and cell-specific regulatory mechanisms of CTBP1 in the context of breast cancer.

This study prioritized CTBP1 in breast cancer by integrating tissue-relevant genetic instruments with genome-wide association study (GWAS) data and exploring cell-type-specific signals. The research was complemented by correlations between gene expression, patient survival data, and magnetic resonance imaging (MRI) radiomics, serving as hypothesis-generating evidence for potential biomarkers. CTBP1 is of particular interest due to its ability to bridge cellular metabolism with transcriptional control and immune regulation. Previous research has demonstrated CTBP1’s role in repressing E-cadherin and modulating redox-sensitive transcription factors,impacting tumor invasiveness and immune evasion. However, its regulation is context-dependent and likely varies across different tissues and cell types. To address these complexities,this study integrates genetic,single-cell,and MRI radiomics data to systematically characterize CTBP1 regulation across multiple biological levels.

Materials and Methods

selection of Hotspot Genes:

A total of 19 succinylation-related genes were selected for this study, as detailed in Supplemental Table S1. The overall workflow is summarized in Supplementary Figure S1.

eQTL Dataset:

Expression quantitative trait loci (eQTL) data for the selected genes were obtained

CTBP1 as a Key Regulator in Breast Cancer: Integrating Genetic, Single-Cell, and Radiomic Data for Prognostic insights

Introduction

Breast cancer continues to be a leading cause of cancer-related mortality among women worldwide, characterized by increasing incidence and complex clinical outcomes.^1-3 Despite advances in early detection and treatment, the unpredictable nature of the disease, stemming from tumor heterogeneity, therapeutic resistance, and immune evasion, necessitates the identification of novel biomarkers for improved risk prediction, prognostic assessment, and personalized therapeutic strategies.^4,5 A growing body of evidence highlights metabolic reprogramming as a fundamental hallmark of cancer initiation and progression.^6,7 Within this landscape,lysine succinylation – a post-translational modification (PTM) – has emerged as a crucial regulator of tumor biology,influencing protein structure,function,gene expression,metabolic flux,and immune signaling.^8-10

While the role of succinylation in cancer is becoming increasingly clear, its specific mechanisms within breast cancer, particularly concerning the interplay with the immune microenvironment and imaging characteristics, remain largely unexplored. This knowledge gap hinders the development of targeted interventions and robust prognostic tools.Thus, a comprehensive prognostic model integrating metabolic information, immune response, and imaging features, centered around succinylation, is of paramount clinical importance.

Carbon catabolite protein 1 (CTBP1) is a particularly compelling target in this context. Extensively studied as a transcriptional corepressor, CTBP1 promotes tumor proliferation, epithelial-mesenchymal transition (EMT), and metastasis through pathways like CDH1 repression and TGF-β signaling.^11-15 Furthermore, CTBP1 interacts with metabolic and chromatin modifiers, establishing a link between redox homeostasis and oncogenic transcriptional programs in breast and other cancers.^11,12 These findings underscore the need to investigate the tissue- and cell-specific regulatory mechanisms of CTBP1 in breast cancer.

This study prioritized CTBP1 in breast cancer by integrating tissue-relevant genetic instruments with genome-wide association study (GWAS) data and exploring cell-type-specific signals. We complemented these analyses with correlations between gene expression, patient survival, and magnetic resonance imaging (MRI) radiomics data, utilizing these findings as hypothesis-generating evidence rather then definitive biomarker identification. CTBP1’s unique position at the intersection of cellular metabolism, transcriptional control, and immune regulation makes it a particularly promising area of investigation. Previous research has demonstrated CTBP1’s ability to repress E-cadherin and modulate redox-sensitive transcription factors, impacting both tumor invasiveness and immune evasion. However, its regulation appears context-dependent and may vary across different tissues or cell types. To address these complexities,our study integrates genetic,single-cell,and MRI radiomics data to systematically characterize CTBP1 regulation across multiple biological levels.

Materials and Methods

Selection of Hotspot Genes

A total of 19 succinylation-related genes were selected for this study,based on prior literature.^9,10,16-18 A comprehensive list of these genes is provided in Supplemental Table S1. The overall workflow of the study is summarized in Supplementary Figure S1.

*e

“`html

Protein Succinylation: A Deep Dive into This Emerging Post-Translational Modification

Introduction to Protein Succinylation

Protein succinylation is a relatively recently discovered post-translational modification (PTM) that’s gaining significant attention in the scientific community.PTMs are crucial for regulating protein function, and succinylation is proving to be a key player in diverse cellular processes. Unlike more well-studied PTMs like phosphorylation or acetylation,succinylation involves the addition of a succinyl group to lysine residues on proteins. This modification isn’t just a biochemical curiosity; it’s increasingly linked to metabolic regulation, signal transduction, and disease development.

The Biochemistry of Succinylation

What is Succinylation?

At its core, succinylation is the enzymatic transfer of a succinyl group (derived from succinyl-CoA) to the ε-amino group of lysine residues within a protein. This reaction is catalyzed by succinyltransferases, with KAT2A being a prominent example. The addition of the succinyl group alters the protein’s charge and structure,perhaps impacting its interactions with other molecules and its overall function.

How Does it Differ from Other PTMs?

while superficially similar to acetylation, succinylation differs in several key aspects. Acetylation utilizes acetyl-coa, while succinylation uses succinyl-CoA, a central intermediate in the Krebs cycle. This connection to metabolism is a defining characteristic of succinylation.Furthermore, succinylation generally exhibits a stronger effect on protein function compared to acetylation, likely due to the larger size and different chemical properties of the succinyl group.

Biological Roles of Protein Succinylation

Metabolic Regulation

Perhaps the most prominent role of succinylation lies in metabolic regulation. Because succinyl-CoA is a key metabolite, the levels of succinylation can directly reflect the metabolic state of the cell. Succinylated proteins often participate in pathways related to glucose metabolism, fatty acid oxidation, and the Krebs cycle itself. This creates a feedback loop where metabolic activity influences protein modification, and vice versa.

Beyond Metabolism: Diverse Cellular Functions

The influence of succinylation extends beyond metabolism. Research indicates roles in:

• Gene Transcription: Succinylation can modulate the activity of transcription factors, influencing gene expression.
• Signal Transduction: Modifying proteins involved in signaling pathways can alter cellular responses to external stimuli.
• Protein-Protein Interactions: Succinylation can disrupt or enhance interactions between proteins, impacting complex formation and function.

Succinylation and Disease

Dysregulation of protein succinylation has been implicated in several diseases, including cancer. For example, studies have shown that succinylation of CTBP1 suppresses its inhibitory activity on CDH1 transcription, promoting prostate cancer progression. 15 Aberrant succinylation patterns have also been observed in neurodegenerative diseases and metabolic disorders.

Methods for Detecting and Studying Succinylation

Antibody-based Approaches

The most common method for detecting succinylation involves using antibodies specifically raised against succinylated lysine residues. Western blotting and immunoprecipitation are frequently employed with these antibodies to identify and quantify succinylated proteins.

Mass Spectrometry

Mass spectrometry provides a more comprehensive and quantitative approach. By analyzing the mass differences between modified and unmodified peptides, researchers can identify succinylation sites with high accuracy. This technique is particularly useful for large-scale proteomic studies.

Emerging Technologies

New technologies are continually being developed to improve the detection and analysis of succinylation, including click chemistry-based methods and improved bioinformatics tools for data interpretation.

Key Takeaways

• Protein succinylation is a dynamic PTM with a strong link to cellular metabolism.
• It involves the addition of a succinyl group to lysine residues, altering protein function.
• Succinylation plays roles in metabolic regulation, gene transcription, signal transduction, and disease development.
• Antibody-based methods and mass spectrometry are key techniques for studying succinylation.

Future Directions

The field of protein succinylation is still in its early stages, and much remains to be discovered. Future research will likely focus on:

• Identifying the full spectrum of proteins that undergo succinylation.
• Elucidating the precise mechanisms by which succinylation regulates protein function.
• Developing targeted therapies that modulate succinylation to treat diseases.
• Understanding the interplay between succinylation and other PTMs.

As our understanding of protein succinylation deepens, it promises