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BMC Cancer

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Open Access 01-12-2023 | Breast Cancer | Research

A novel super-enhancer-related gene signature predicts prognosis and immune microenvironment for breast cancer

Authors: Qing Wu, Xuan Tao, Yang Luo, Shiyao Zheng, Nan Lin, Xianhe Xie

Published in: BMC Cancer | Issue 1/2023

Abstract

Background

This study targeted at developing a robust, prognostic signature based on super-enhancer-related genes (SERGs) to reveal survival prognosis and immune microenvironment of breast cancer.

Methods

RNA-sequencing data of breast cancer were retrieved from The Cancer Genome Atlas (TCGA), 1069 patients of which were randomly assigned into training or testing set in 1:1 ratio. SERGs were downloaded from Super-Enhancer Database (SEdb). After which, a SERGs signature was established based on the training set, with its prognostic value further validated in the testing set. Subsequently, we identified the potential function enrichment and tumor immune infiltration of the model. Moreover, in vitro experiments were completed to further explore the biological functions of ZIC2 gene (one of the risk genes in the prognostic model) in breast cancer.

Results

A risk score system of prognostic value was constructed with 6 SERGs (ZIC2, NFE2, FOXJ1, KLF15, POU3F2 and SPIB) to find patients in high-risk group with significantly worse prognosis in both training and testing sets. In addition, a multivariate regression was established via integrating the 6 genes with age and N stage, indicating well performance by calibration, time-dependent receiver operating characteristic (ROC) analysis and decision curve analysis (DCA). Further analysis demonstrated that tumor-associated pathological processes and pathways were significantly enriched in the high-risk group. In general, the novel SERGs signature could be applied to screen breast cancer with immunosuppressive microenvironment for the risk score was negatively correlated with ESTIMATE score, tumor-infiltration lymphocytes (such as CD4 + and CD8 + T cell), immune checkpoints and chemotactic factors. Furthermore, down-regulation of ZIC2 gene expression inhibited the cell viability, cellular migration and cell cycle of breast cancer cells.

Conclusions

The novel SERGs signature could predict the prognosis of breast cancer; and SERGs might serve as potential therapeutic targets for breast cancer.

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Title: A novel super-enhancer-related gene signature predicts prognosis and immune microenvironment for breast cancer
Authors: Qing Wu
Xuan Tao
Yang Luo
Shiyao Zheng
Nan Lin
Xianhe Xie
Publication date: 01-12-2023
Publisher: BioMed Central
Keywords: Breast Cancer
Breast Cancer
Published in: BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-023-11241-2

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

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Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

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