Development and validation of a mitotic catastrophe-related genes prognostic model for breast cancer

Abstract

Background Breast cancer has become the most common malignant tumor in women worldwide. Mitotic catastrophe (MC) is a way of cell death that plays an important role in the development of tumors. However, the exact relationship between MC-related genes (MCRGs) and the development of breast cancer is still unclear, and further research is needed to elucidate this complexity. Methods Transcriptome data and clinical data of breast cancer were downloaded from the Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database. We identified differential expression of MCRGs by comparing tumor tissue with normal tissue. Subsequently, we used COX regression analysis and LASSO regression analysis to construct the prognosis risk model of MCRGs. Kaplan–Meier survival curve and receiver operating characteristic (ROC) curve were used to evaluate the predictive ability of prognostic model. Moreover, the clinical relevance, gene set enrichment analysis (GSEA), immune landscape, tumor mutation burden (TMB), and immunotherapy and drug sensitivity analysis between high-risk and low-risk groups were systematically investigated. Finally, we validated the expression levels of genes involved in constructing the prognostic model through real-time quantitative polymerase chain reaction (RT-qPCR) at the cellular and tissue levels. Results We identified 12 prognostic associated MCRGs, four of which were selected to construct prognostic model. The Kaplan-Meier analysis suggested that patients in the high-risk group had a shorter overall survival (OS). The Cox regression analysis and ROC analysis indicated that risk model had independent and excellent ability in predicting prognosis of breast cancer patients. Mechanistically, a remarkable difference was observed in clinical relevance, GSEA, immune landscape, TMB, immunotherapy response, and drug sensitivity analysis. RT-qPCR results showed that genes involved in constructing the prognostic model showed significant abnormal expressions and the expression change trends were consistent with the bioinformatics results. Conclusions We established a prognosis risk model based on four MCRGs that had the ability to predict clinical prognosis and immune landscape, proposing potential therapeutic targets for breast cancer.

Keywords

• Breast cancer
• Mitotic catastrophe
• Immune microenvironment
• Bioinformatics