Abstract
This study was designed to identify an immune-related gene signature (IRGS) associated with breast cancer (BC) patient outcomes. Transcriptomic data from 1411 BC patients in the TCGA and GEO databases were used to identify differentially expressed immune-related genes (DEIGs) when comparing BC tumor and normal tissue samples. We were able to construct a 27-gene IRGS that was able to effectively separate BC patients into high- and low-risk groups that corresponded to significant differences in overall and recurrence-free survival (OS and RFS, respectively). Besides, the relevance of this signature to immune response and immune cell infiltration of BC tumors was evaluated. These high- and low-risk BC patients were found to exhibit significantly different immune responses and functional enrichment. We also identified patients in the high-risk group exhibited significantly reduced immune cell infiltration of tumors relative to low-risk patients. Together, the results of this analysis offer a novel overview of the immune microenvironment within BC tumors and highlight key immunological genes associated with patient survival outcomes.
Highlights
Breast cancer (BC) remains the most common form of cancer globally [1]
An IRGSbased prognostic risk score was assigned based on the following formula: Risk score = expression of Gene 1 ∗ β1 + expression of Gene 2 ∗ β2 +. . . expression of Gene n ∗ βn, with β corresponding to gene-specific regression coefficient values that were generated based on our The Cancer Genome Atlas (TCGA) training dataset
The prognostic relevance of differentially expressed immune-related genes (DEIGs) was assessed via univariate Cox regression analyses, with hazard ratio (HR) values being used to determine the association between DEIG expression and patient risk
Summary
Breast cancer (BC) remains the most common form of cancer globally [1]. There have been numerous diagnostic and therapeutic improvements over the past 30 years that have facilitated a ∼33% reduction in BC mortality [2]. Preclinical studies in recent years have clearly demonstrated that both local inflammation and the immune landscape of the tumor stromal compartment can influence tumor development and progression [4, 5]. This has led to an increasing focus on the identification of specific immunerelated genes or gene signatures that can offer insight into BC progression and/or therapeutic susceptibility. The specific composition of the immunological component of the BC TME is, at present, poorly understood, as few studies have conducted a thorough examination of the dynamics of immune cell infiltration into BC tumors or the plasticity of their responses therein owing to the difficulties inherent in such analyses. Our results highlight a novel overview of the immune microenvironment within BC tumors and highlight key immunological pathways associated with patient survival outcomes
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