Integrated Pan-Cancer Analysis and Experimental Verification of the Roles of Retinoid-Binding Proteins in Breast Cancer

TL;DR

This study explores how vitamin A-related proteins, especially RBP4 and RBP7, behave in various cancers and how they might help predict outcomes and guide new breast cancer treatments.

Contribution

The study provides a pan-cancer analysis of retinoid-binding proteins and identifies RBP4 and RBP7 as potential prognostic biomarkers in breast cancer.

Findings

RBP7 shows patterns linked to better outcomes in several cancers, including breast cancer.

RBP4 and RBP7 expression varies with tumor stage and grade across multiple cancers.

RBP4 and RBP7 are identified as protective genes in specific cancers like breast cancer and uveal melanoma.

Abstract

Many cancers disrupt how vitamin A-related proteins control cell growth and death. We studied these proteins, especially RBP4 and RBP7, to learn how their levels differ across cancers and what that means for patients, with special attention to triple-negative breast cancer, a difficult-to-treat subtype. Using large cancer datasets and single-cell analysis, we mapped where these proteins are reduced, how they change with tumor stage and grade, and how they relate to survival. We found that RBP7 shows patterns linked to better outcomes in several cancers, including breast cancer. Our goal is to identify which patients could benefit from using these proteins as markers to predict prognosis and to guide the design of new treatments. These results give researchers a clearer picture of the tumor environment and provide testable targets for future laboratory and clinical studies.

Background: Retinoid-binding proteins (RBPs) regulate retinoid metabolism and signaling, but their roles across human cancers remain incompletely defined. Methods: We conducted a comprehensive analysis using bioinformatics tools and experimental validations, examining RBP expression profiles across cancer types based on data from The Cancer Genome Atlas (TCGA). We employed survival analysis using the Kaplan–Meier method and utilized single-cell RNA sequencing (scRNA-seq) to investigate the roles of RBP4 and RBP7 in the tumor microenvironment. Results: Our analysis revealed significant downregulation of RBPs in multiple cancers, with RBP4 and RBP7 showing notable expression variations linked to tumor stages and grades. Cox analysis identified RBP4 as a protective gene in kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), and mesothelioma (MESO), while RBP7 exhibited protective effects in breast cancer (BRCA) and uveal melanoma (UVM). Conclusions: This pan-cancer and single-cell integrative analysis highlights the complex roles of RBPs in cancer progression and their potential as prognostic biomarkers, particularly RBP4 and RBP7 in breast cancer. These findings warrant further investigation into the functional mechanisms of RBPs, which may provide valuable strategies for therapeutic interventions.

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