Prognostic significance and regulatory role of ACOT7 in the tumor immune microenvironment of breast invasive ductal carcinoma: a multi-omics analysis

TL;DR

This study explores how ACOT7, a protein involved in cell metabolism, is linked to worse outcomes in breast cancer and how it affects the tumor's immune environment.

Contribution

The study reveals ACOT7's role in tumor immune infiltration and metabolic pathways in breast invasive ductal carcinoma.

Findings

ACOT7 expression is significantly higher in IDC tumors compared to normal tissues.

High ACOT7 levels correlate with poorer survival and increased immune infiltration in IDC.

ACOT7 is involved in metabolic and immune-related pathways linked to cancer progression.

Abstract

Invasive Ductal Carcinoma (IDC), which is the most common histological subtype of breast cancer, is highly aggressive and progresses rapidly. Acyl-CoA thioesterase 7 (ACOT7) is a key regulator of cell survival, the cell cycle, and lipid and glucose metabolism. However, the mechanism of ACOT7 in IDC is still unclear. Our study aims to investigate the clinical significance of ACOT7 in IDC.

A comparative analysis of ACOT7 expression in IDC and matched normal tissues was performed using the limma R package on datasets from GEO and TCGA. Prognostic evaluation was conducted using Kaplan-Meier survival curves from the Kaplan-Meier plotter. Furthermore, a protein-protein interaction (PPI) network of ACOT7 was constructed by GeneMANIA, and the correlation between ACOT7 expression and the level of tumor immune infiltration was explored via the TIMER database. In order to further analyze the biological functions of ACOT7, we performed Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and Gene Set Enrichment Analysis (GSEA) using the clusterProfiler package. To validate this, we profiled ACOT7 mRNA expression across clinical samples (tumor and adjacent normal) and in vitro models (cell lines) via Real-Time quantitative Polymerase Chain Reaction (RT-qPCR).

Bioinformatic analysis of public databases revealed that ACOT7 mRNA expression was significantly upregulated in IDC patients compared to normal tissues. Elevated ACOT7 expression was associated with poorer overall survival, a finding further validated in cell lines and clinical tissue samples. Furthermore, ACOT7 transcriptional levels showed a significant correlation with the degree of tumor immune infiltration. Functional enrichment analysis indicated that ACOT7 is primarily involved in cancer-related regulation, autoimmune diseases, and multiple metabolic pathways.

Our study indicates that elevated ACOT7 expression is a significant marker of adverse clinical outcomes. This effect it likely mediated through the remodeling of the tumor immune microenvironment and the reprogramming of metabolic pathways, which collectively fuel the malignant procession of IDC. These results provide a solid theoretical foundation for targeting ACOT7 as both a prognostic biomarker and a potential therapeutic target in IDC.

Figures