Abstract
Objective Tumor microenvironment as an important element of malignancy could help predict cancer prognosis and therapeutic response; thus, a prognostic landscape map of the tumor microenvironment in luminal B breast cancers should be developed. Methods The GEO and TCGA databases were employed to retrieve clinical follow-up data and expression profiles of luminal B breast cancer. CIBERSORT was applied to assess the infiltration of the tumor microenvironment of 209 patients and to construct tumor microenvironment-based subtypes of luminal B breast cancer. We also conducted Cox multivariate regression analysis to select features that could be used to develop a microenvironment signature for cancer. Samples were categorized as having low and high TME scores according to the median TME score. The correlations of prognosis and TME score, expression levels of immune factors and genomic variation, and clinical features were further investigated. Results We found that high TME scores were correlated with poor prognosis. The current findings showed that the expressions of multiple immune-related genes, including CXCL9, CXCL10, GZMB, and PDCD1LG2, were upregulated in cancer with high TME scores. The high-risk group showed lower TP53 gene mutation frequency as opposed to that of the low-risk group. For the purpose of developing a TME scoring system, the TME infiltration levels of 209 patients with luminal B breast cancer from TCGA were comprehensively analyzed. Conclusions Our analysis revealed that the TME score was an indicator of patients' response to immune checkpoint modulators and an effective prognostic biomarker. TME scoring improves current immunotherapy on luminal B breast cancer.
Highlights
Statistics on breast cancer showed that in 2018, over 2.1 million cases of breast cancer were recorded, resulting in about 630,000 breast cancer deaths [1]
The results showed that the scores of M2 macrophages and activated mast cells were strongly associated with an unfavorable prognosis
The results demonstrated that immune cells, such as naïve B cells and regulatory T cell (Treg) scores, were noticeably higher in TMEC1 and that M1 macrophages M1 and CD4 T cells scores were greatly higher in TMEC2
Summary
Statistics on breast cancer showed that in 2018, over 2.1 million cases of breast cancer were recorded, resulting in about 630,000 breast cancer deaths [1]. TMEs have been found to support tumorigenesis, as they could influence immune cell activation, which in turn promote tumor growth and progression [6]. Multiple studies showed that TME is involved in the progression of cancer and patients’ responsiveness to therapy [7, 8]. Previous cancer studies detected differences in components of resident cell types in TME, such as mesenchymal stem cells, tumor-associated macrophages, cytotoxic T cells, dendritic cells (DCs), helper T cells, and associated inflammatory pathways [9,10,11,12]. Alterations in the proportions of infiltrating macrophages, CD8+ T cells, fibroblasts, and CD4+ T cells, in TME are associated with clinical progression of cancer and may be prognostically
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