Abstract
In the microenvironment of breast cancer, immune cell infiltration is associated with an improved prognosis. To identify immune-related prognostic markers and therapeutic targets, we determined the lymphocyte-specific kinase (LCK) metagene scores of samples from breast cancer patients in The Cancer Genome Atlas. The LCK metagene score correlated highly with other immune-related scores, as well as with the clinical stage, prognosis and tumor suppressor gene mutation status (BRCA2, TP53, PTEN) of patients in the four breast cancer subtypes. A weighted gene co-expression network analysis was performed to detect representative genes from LCK metagene-related gene modules. In two of these modules, the levels of the co-expressed genes correlated highly with LCK metagene levels, so we conducted an enrichment analysis to discover their functions. We also identified differentially expressed genes in samples with high and low LCK metagene scores. By examining the overlapping results from these analyses, we obtained 115 genes, and found that 22 of them were independent predictors of overall survival in breast cancer patients. These genes were validated for their prognostic and diagnostic value with external data sets and paired tumor and non-tumor tissues. The genes identified herein could serve as diagnostic/prognostic markers and immune-related therapeutic targets in breast cancer.
Highlights
In recent years, with the increasing understanding of the immune microenvironment of breast cancer tissues, immune escape has come to be considered an important marker of breast cancer development [1,2,3,4]
We analyzed the distribution of lymphocyte-specific kinase (LCK) metagene levels in patients of the four breast cancer subtypes at different clinical stages (Figure 2A–2D)
LCK metagene expression was significantly upregulated in stage I in triple-negative breast cancer (TNBC), suggesting that high LCK metagene expression may be a positive prognostic factor in TNBC
Summary
With the increasing understanding of the immune microenvironment of breast cancer tissues, immune escape has come to be considered an important marker of breast cancer development [1,2,3,4]. Tumor cells continuously interact with the immune microenvironment and gradually acquire the capacity for immune escape [5]. Both innate immunity (facilitated by macrophages and neutrophils) and adaptive immunity (facilitated by T cells and B cells) are impaired in patients with breast cancer. These impairments alter the immune microenvironment and promote the occurrence and development of tumors by (1) stimulating tumor angiogenesis, (2) altering the biological characteristics of tumors, (3) screening for tumor cells that are more suitable for survival in the host microenvironment and (4) regulating the activity of tumor stem cells. Such research has mostly been limited to preclinical experiments or clinical data-mining studies with small sample sizes [7]
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