Abstract
The aim of this study was to reveal genes associated with breast cancer metastasis, to investigate their intrinsic relationship with immune cell infiltration in the tumor microenvironment, and to screen for prognostic biomarkers. Gene expression data of breast cancer patients and their metastases were downloaded from the GEO, TCGA database. R language package was used to screen for differentially expressed genes, enrichment analysis of genes, PPI network construction, and also to elucidate key genes for diagnostic and prognostic survival. Spearman’s r correlation was used to analyze the correlation between key genes and infiltrating immune cells. We screened 25 hub genes, FN1, CLEC5A, ATP8B4, TLR7, LY86, PTGER3 and other genes were differentially expressed in cancer and paraneoplastic tissues. However, patients with higher expression of CD1C, IL-18 breast cancer had a better prognosis in the 10 years survival period, while patients with high expression of FN1, EIF4EBP1 tumors had a worse prognosis. In addition, TP53 and HIF1 genes are closely related to the signaling pathway of breast cancer metastasis. In this study, gene expression of ATP8B4 and CD1C were correlated with cancer tissue infiltration of CD8+ T lymphocytes, while GSE43816, GSE62327 and TCGA databases showed that CD8+ T lymphocytes were closely associated with breast cancer progression. Functional enrichment analysis of genes based on expression differences yielded key genes of prognostic value in the breast cancer microenvironment.
Highlights
Breast cancer is the most common malignancy in women worldwide and the most common cancer surpassed lung cancer (Sung et al, 2021)
When we take the dataset of The Cancer Genome Atlas (TCGA) chemotherapy and metastasis and the GSE dataset to intersect, there were totally 74 upregulated mRNAs that were commonly found in four datasets (Fig. 2B)
Analysis of expression levels based on key genes and survival analysis in TCGA breast cancers To further confirm the expression of hub genes in breast cancer, we examined the expression of 25 hub genes in TCGA database and subjected these genes to correlation analysis of TCGA expression in breast cancer, we found that in the screened differential genes TLR7, LY86, CLEC5A, CXCR4, PARP1, FN1 were expressed at lower levels in breast cancer cancer than in the paracancer
Summary
Breast cancer is the most common malignancy in women worldwide and the most common cancer surpassed lung cancer (Sung et al, 2021). Great progress has been made in the comprehensive treatment of breast cancer, such as targeted anti-HER2 therapy and endocrine therapy, but the prognosis of patients is still not very optimistic (Qiu et al, 2021; Yuan et al, 2020). Since metastasis of breast cancer seriously affects the prognosis of patients, we still do not fully understand the underlying molecular mechanisms of Currently, numerous studies have confirmed that tumorigenesis, progression and prognosis are closely related to tumor tissue gene expression (Li et al, 2021b; Lin et al, 2017; Zhang et al, 2019). Studies had found that altered gene expression in tumor tissue might lead to changes in non-tumor cell infiltration.
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