Research Paper Volume 16, Issue 2 pp 1581—1604

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

Tao Xie1,2, *, , Du-Jiang Fu1, *, , Kang-Jing Li1, *, , Jia-Ding Guo2, , Zhao-Ming Xiao2, , Zhijie Li3, , Shan-Chao Zhao1,2, ,

  • 1 Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
  • 2 Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510500, China
  • 3 Department of Geriatric Medicine, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, China
* Equal contribution

Received: August 23, 2023       Accepted: December 1, 2023       Published: January 17, 2024      

https://doi.org/10.18632/aging.205445
How to Cite

Copyright: © 2024 Xie et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Basement membrane plays an important role in tumor invasion and metastasis, which is closely related to prognosis. However, the prognostic value and biology of basement membrane genes (BMGs) in prostate cancer (PCa) remain unknown. In the TCGA training set, we used differentially expressed gene analysis, protein-protein interaction networks, univariate and multivariate Cox regression, and least absolute shrinkage and selection operator regression to construct a basement membrane-related risk model (BMRM) and validated its effectiveness in the MSKCC validation set. Furthermore, the accurate nomogram was constructed to improve clinical applicability. Patients with PCa were divided into high-risk and low-risk groups according to the optimal cut-off value of the basement membrane-related risk score (BMRS). It was found that BMRS was significantly associated with RFS, T-stage, Gleason score, and tumor microenvironmental characteristics in PCa patients. Further analysis showed that the model grouping was closely related to tumor immune microenvironment characteristics, immune checkpoint inhibitors, and chemotherapeutic drug sensitivity. In this study, we developed a new BMGs-based prognostic model to determine the prognostic value of BMGs in PCa. Finally, we confirmed that THBS2, a key gene in BMRM, may be an important link in the occurrence and progression of PCa. This study provides a novel perspective to assess the prognosis of PCa patients and provides clues for the selection of future personalized treatment regimens.

Abbreviations

PCa: Prostate cancer; ECM: Extracellular matrix; BMGs: Basement membrane genes; TIME: Tumor immune microenvironment; RFS: Recurrence-free survival; DEGs: Differentially expressed genes; DE-BMGs: Differentially expressed basement membrane genes; BMRM: Basement membrane-related risk models; BMRS: Basement membrane-related risk score; TIDE: Tumor immune dysfunction and exclusion; CNV: Copy number variation; TMB: Tumor mutation burden; MMPs: Matrix metalloproteinases; ICIs: Immune checkpoint inhibitors; TAMs: Tumor-associated macrophages; GO: Gene ontology; KEGG: Kyoto encyclopedia of genes and genomes; GSEA: Gene set registration analysis; PPI: Protein-protein interaction; HR: Hazard ratio; AUC: Area under curve; ROC: Receiver operating characteristic; CCK-8: Cell Counting Kit-8.