The prognostic significance and immune characteristics of bone morphogenetic proteins (BMPs) family: A pan-cancer multi-omics analysis

Article type: Research Article

Authors: Chen, Changsheng^{a; b; c; 1} | Zhang, Yu^{a; b; d; 1} | Lin, Yuda^{a; b; 1} | Shen, Chong^{a; b; *} | Zhang, Zhe^{a; b} | Wu, Zhouliang^{a; b} | Qie, Yunkai^{a; b} | Zhao, Gangjian^{a; b} | Hu, Hailong^{a; b; *}

Affiliations: [a] Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China | [b] Tianjin Key Laboratory of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China | [c] Department of Urology, Tianjin Haihe Hospital, Tianjin, China | [d] Department of Urology, The Eco-City Hospital of Tianjin Fifth Central Hospital, Tianjin, China

Correspondence: [*] Corresponding authors: Chong Shen and Hailong Hu, Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, No. 23, Pingjiang Road, Tianjin 300211, China. E-mail: shenchong20160806@163.com and huhailong@tmu.edu.cn.

Note: [1] These authors contributed equally to this work.

Abstract: BACKGROUND: Bone morphogenetic proteins (BMPs) are a group of cancer-related proteins vital for development and progression of certain cancer types. Nevertheless, function of BMP family in pan-cancer was not detailedly researched. OBJECTIVE: Investigating expression pattern and prognostic value of the BMPs family (BMP1-8A and BMP8B) expression across multiple cancer types. METHODS: Our research integrated multi-omics data for exploring potential associations between BMPs expression and prognosis, clinicopathological characteristics, copy number or somatic mutations, immune characteristics, tumor microenvironment (TME), tumor mutation burden (TMB), microsatellite instability (MSI), immune checkpoint genes and drug sensitivity in The Cancer Genome Atlas (TCGA) tumors. Furthermore, association of BMPs expression and immunotherapy effectiveness was investigated in some confirmatory cohorts (GSE111636, GSE78220, GSE67501, GSE176307, IMvigor210 and mRNA sequencing data from currently undergoing TRUCE01 clinical research included), and biological function and potential signaling pathways of BMPs in bladder cancer (BCa) was explored via Gene Set Enrichment Analysis (GSEA). Eventually, immune infiltration analysis was done via BMPs expression, copy number or somatic mutations in BCa, as well as validation of the expression levels by reverse transcription-quantitative PCR and western blot, and in vitro functional experiments of BMP8A. RESULTS: Discoveries displayed BMPs expression was related to prognosis, clinicopathological characteristics, mutations, TME, TMB, MSI and immune checkpoint genes of TCGA tumors. Anticancer drug sensitivity analysis displayed BMPs were associated with various drug sensitivities. What’s more, it was discovered that expression level of certain BMP family members related to objective response to immunotherapy. By GSEA, we discovered multiple immune-associated functions and pathways were enriched. Immune infiltration analysis on BCa also displayed significant associations among BMPs copy number variations, mutation status and infiltration level of diverse immune cells. Furthermore, differential expression validation and in vitro phenotypic experiment indicated that BMP8A significantly promoted BCa cell proliferation, migration and invasion. CONCLUSIONS: Current results confirmed significance of both BMPs expression and genomic alteration in the prognosis and treatment of diverse cancer types, and suggested that BMPs may be vital for BCa and can possibly be utilized as biomarkers for immunotherapy.

Keywords: Bone morphogenetic proteins, pan-cancer analysis, bladder cancer, tumor microenvironment, prognosis

DOI: 10.3233/THC-232004

Journal: Technology and Health Care, vol. 32, no. 6, pp. 4123-4175, 2024