Abstract
BackgroundBreast cancer is one of the most frequently diagnosed cancers among women worldwide. Alterations in the tumor microenvironment (TME) have been increasingly recognized as key in the development and progression of breast cancer in recent years. To deeply comprehend the gene expression profiling of the TME and identify immunological targets, as well as determine the relationship between gene expression and different prognoses is highly critical.MethodsThe stromal/immune scores of breast cancer patients from The Cancer Genome Atlas (TCGA) were employed to comprehensively evaluate the TME. Then, TME characteristics were assessed, overlapping genes of the top 3 Gene Ontology (GO) terms and upregulated differentially expressed genes (DEGs) were analyzed. Finally, through combined analyses of overall survival, time-dependent receiver operating characteristic (ROC), and protein-protein interaction (PPI) network, novel immune related genes with good prognosis were screened and validated in both TCGA and GEO database.ResultsAlthough the TME did not correlate with the stages of breast cancer, it was closely associated with the subtypes of breast cancer and gene mutations (CDH1, TP53 and PTEN), and had immunological characteristics. Based on GO functional enrichment analysis, the upregulated genes from the high vs low immune score groups were mainly involved in T cell activation, the external side of the plasma membrane, and receptor ligand activity. The top GO terms of the upregulated DEGs from the high vs low immune score groups exhibited better prognosis in breast cancer; 15 of them were related to good prognosis in breast cancer, especially CD226 and KLRC4-KLRK1.ConclusionsHigh CD226 and KLRC4-KLRK1 expression levels were identified and validated to correlate with better overall survival in specific stages or subtypes of breast cancer. CD226, KLRC4-KLRK1 and other new targets seem to be promising avenues for promoting antitumor targeted immunotherapy in breast cancer.
Highlights
Breast cancer is one of the most frequently diagnosed cancers among women worldwide
Data sources and preprocessing RNA sequencing (RNA-seq) data in fragments per kilobase of transcript per million mapped reads (FPKM), single-nucleotide polymorphism data and clinical followup information such as age, molecular subtype, outcome and survival time of breast cancer were downloaded from The Cancer Genome Atlas (TCGA) database
Immune scores and stromal scores are closely related to breast cancer subtypes but not associated with breast cancer stages In our study, the stromal scores ranged from − 2164.14 to 2050.55, and the immune scores were distributed between − 1724.88 and 3459.35
Summary
Alterations in the tumor microenvironment (TME) have been increasingly recognized as key in the development and progression of breast cancer in recent years. Breast cancer is one of the most frequently diagnosed cancers among women worldwide [1]. Multidisciplinary approaches, including chemotherapy, endocrine therapy, molecular targeted therapy, radiotherapy, and surgery, are commonly used to improve breast cancer patient survival. Not all patients benefit from combined treatment, and as many as 40% of women with breast cancer will still be resistant to currently available targeted therapy approaches [4]. Obvious alterations in the tumor microenvironment (TME) have been increasingly recognized as key in the development and progression of breast cancer
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