Identification of a basement membrane-related gene signature for predicting prognosis and estimating the tumor immune microenvironment in breast cancer

Abstract

Introduction: Breast cancer (BC) is the most common malignancy in the world and has a high cancer-related mortality rate. Basement membranes (BMs) guide cell polarity, differentiation, migration and survival, and their functions are closely related to tumor diseases. However, few studies have focused on the association of basement membrane-related genes (BMRGs) with BC. This study aimed to explore the prognostic features of BMRGs in BC and provide new directions for the prevention and treatment of BC. Methods: We collected transcriptomic and clinical data of BC patients from TCGA and GEO datasets and constructed a predictive signature for BMRGs by using univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis. The reliability of the model was further evaluated and validated by Kaplan-Meier survival curves and receiver operating characteristic curves (ROC). Column line plots and corresponding calibration curves were constructed. Possible biological pathways were investigated by enrichment analysis. Afterward, we assessed the mutation status by tumor mutational burden (TMB) analysis and compared different subtypes using cluster analysis. Finally, we examined drug treatment sensitivity and immunological correlation to lay the groundwork for more in-depth studies in this area. Results: The prognostic risk model consisted of 7 genes (FBLN5, ITGB2, LAMC3, MMP1, EVA1B, SDC1, UNC5A). After validation, we found that the model was highly reliable and could accurately predict the prognosis of BC patients. Cluster analysis showed that patients with cluster 1 had more sensitive drugs and had better chances of better clinical outcomes. In addition, TMB, immune checkpoint, immune status, and semi-inhibitory concentrations were significantly different between high and low-risk groups, with lower-risk patients having the better anti-cancer ability. Discussion: The basement membrane-related gene signature that we established can be applied as an independent prognostic factor for BC and can provide a reference for individualized treatment of BC patients.