Bone morphogenetic protein 1 as a macromolecular pan-cancer biomarker modulating the immune microenvironment and malignant phenotypes in glioblastoma

Abstract

Bone morphogenetic protein 1 (BMP1), a member of the astacin metalloprotease superfamily, is frequently overexpressed in various cancers, yet its precise role in glioblastoma (GBM) progression and the tumor microenvironment remains poorly understood. To address this, we performed a comprehensive analysis of BMP1 expression across multiple cancer types using publicly available datasets, including TCGA, CGGA, GEO, CPTAC, TISCH, HPA, and SpatialTME. Single-cell RNA sequencing and spatial transcriptomics were employed to investigate BMP1 localization and its interactions with immune cells, revealing significant associations with macrophages and fibroblasts. Gene set enrichment analysis identified key pathways linked to BMP1, including those involved in cell proliferation, invasion, and immune regulation. Through molecular docking, dynamic simulations, and connectivity map screening, we identified AH.6809 as a compound that stably binds to BMP1. In vitro experiments demonstrated that both BMP1 knockdown and AH.6809 treatment effectively suppressed GBM cell malignancy and induced apoptosis. Furthermore, in a subcutaneous tumor model, AH.6809 significantly inhibited tumor growth, underscoring its potential as a therapeutic agent. BMP1 emerges as a prognostic biomarker and potential immunotherapeutic target in GBM, with AH.6809 demonstrating stable binding to BMP1 and therapeutic promise in BMP1-overexpressing cancers.

Keywords: BMP1; Glioblastoma; Spatial transcriptomics.