Identification of novel a chromatin regulator signature predicting overall survival for breast cancer

Abstract

Background Breast cancer (BRCA) has the highest incidence among female malignancies. Increasing evidence has confirmed that chromatin regulators (CRs) are involved in cancer progression. We aim to develop a chromatin regulators signature to predict the prognosis of BRCA patients. Methods The mRNA expression profiles and corresponding clinical data of BRCA patients were downloaded from TCGA databases, and then the differentially expressed CRs genes were screened. We also used the least absolute shrinkage and selection operator (LASSO) Cox regression model to construct a multigene signature with CRs genes of BRCA patients and evaluated the efficacy of the CRs prognostic signature with GEO validation cohort. Then, we explored the differences of tumor immune cell infiltration, tumor mutation burden (TMB), and patients’ response to chemotherapy between the different risk group. Results This CRs prognostic signature consisted of 8 chromatin regulators related genes, which was an independent prognostic factor of BRCA. The prognostic signature was further validated in GSE42568 cohort. According to the signature, patients with BRCA were divide into two risk groups. Functional annotation and the pathway analysis showed that the high-risk group had an enrichment of many tumor features, including cGMP-PKG signaling pathway, chromatin remodeling, DNA repair, thyroid cancer, cell cycle, homologous recombination, lysine degradation, pathways in cancer. Moreover, the immune cell types of tumor immune microenvironment and the TMB value of patients in the high-risk group was significantly different from those in low-risk group. ROC curves and nomogram indicated that the risk score had a good accuracy for predicting the survival of BRCA patients. Conclusions We identified a novel CRs prognostic signature which could precisely predict the prognosis of breast cancer patients. Our work elucidated that the CRs genes may serve as an indispensable player in complexity and diversity of tumor progression.