Abstract

Early growth response proteins (EGRs), a transcriptional regulatory family comprised of EGR1, EGR2, EGR3, and EGR 4, are reportedly involved in a vast array of functions. However, EGRs, as a whole, are rarely studied in breast cancer cases. This research was performed based on public datasets. The results demonstrated that, except EGR4, the other EGRs were differentially expressed genes in breast cancer. Subsequently, this study determined the prognosis significance of the EGR family, higher expression levels of EGRs indicating better overall survival (OS) and disease-free survival (DFS), except EGR4. So we attempted to explore the potential mechanism behind the prognostic value of EGRs. At the DNA level, however, neither DNA methylation status nor genetic alterations of EGRs contributed to the prognosis significance. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that EGRs were involved in several immune-related functions. Afterward, we assessed the correlation between EGRs and the immune system before establishing a risk prediction model with a 14-gene immune signature associated with EGRs, a prognostic nomogram predicting individuals’ 1-, 3-, and 5-year survival probabilities. The risk score was an independent prognosis predictor in the breast cancer cohorts. This study evidenced EGRs’ significance for tumor immunity, demonstrating that the EGR family may be a potential immunotherapeutic target for breast cancer. The 14-gene immune signature is a promising prognostic biomarker in breast cancer.

Highlights

  • IntroductionThe tumor microenvironment has become a promising field with fast development

  • In cancer research, the tumor microenvironment has become a promising field with fast development

  • As indicated by the results, the transcriptional levels of EGR1, EGR2, and EGR3 were significantly reduced in patients with breast invasive carcinoma (BRCA) (p < 0.05), whereas the expression level of EGR4 was very low in both breast cancer and normal breast tissues (Figure 1A)

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Summary

Introduction

The tumor microenvironment has become a promising field with fast development. Almost all types of carcinoma are divided into different subtypes by immune genes and tumor-infiltrating immune cells. Significant breakthroughs of immunotherapy have been demonstrated in some cancer categories, such as melanoma and non-small-cell lung cancer (NSCLC). Immunotherapy works by enhancing the immune machinery of the patient to identify cancer as a foreign antigen, which would destroy the cancer cells. Though breast cancer was regarded as an “immune cold tumor,” an increasing number of reports about this field in breast cancer have emerged over the past few years. Patients with certain subtypes of breast cancer would benefit from immunotherapy

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