Comprehensive research into prognostic and immune signatures of transcription factor family in breast cancer.

Background: Breast cancer (BRCA) is the most common malignancy with high morbidity and mortality in women, and transcription factor (TF) is closely related to the occurrence and development of BRCA. This study was designed to identify a prognostic gene signature based on TF family to reveal immune characteristics and prognostic survival of BRCA.

Methods: In this study, RNA-sequence with corresponding clinical data were obtained from The Cancer Genome Atlas (TCGA) and GSE42568. Prognostic differentially expressed transcription factor family genes (TFDEGs) were screened to construct a risk score model, after which BRCA patients were stratified into low-risk and high-risk groups based on their corresponding risk scores. Kaplan-Meier (KM) analysis was applied to evaluate the prognostic implication of risk score model, and a nomogram model was developed and validated with the TCGA and GSE20685. Furthermore, the GSEA revealed pathological processes and signaling pathways enriched in the low-risk and high-risk groups. Finally, analyses regarding levels of immune infiltration, immune checkpoints and chemotactic factors were all completed to investigate the correlation between the risk score and tumor immune microenvironment (TIME).

Results: A prognostic 9-gene signature based on TFDEGs was selected to establish a risk score model. According to KM analyses, high-risk group witnessed a significantly worse overall survival (OS) than low-risk group in both TCGA-BRCA and GSE20685. Furthermore, the nomogram model proved great possibility in predicting the OS of BRCA patients. As indicted in GSEA analysis, tumor-associated pathological processes and pathways were relatively enriched in high-risk group, and the risk score was negatively correlated with ESTIMATE score, infiltration levels of CD4+ and CD8+T cells, as well as expression levels of immune checkpoints and chemotactic factors.

Conclusions: The prognostic model based on TFDEGs could distinguish as a novel biomarker for predicting prognosis of BRCA patients; in addition, it may also be utilized to identify potential benefit population from immunotherapy in different TIME and predict potential drug targets.