Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.
Tianjin Key Laboratory of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.
Technol Health Care. 2024;32(6):4123-4175. doi: 10.3233/THC-232004.
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.
Investigating expression pattern and prognostic value of the BMPs family (BMP1-8A and BMP8B) expression across multiple cancer types.
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.
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.
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.
骨形态发生蛋白（BMPs）是一组与癌症相关的蛋白质，对某些癌症类型的发生和发展至关重要。然而，BMP 家族在泛癌症中的功能尚未详细研究。
研究 BMP 家族（BMP1-8A 和 BMP8B）在多种癌症类型中的表达模式和预后价值。
我们的研究整合了多组学数据，以探索 BMPs 表达与预后、临床病理特征、拷贝数或体细胞突变、免疫特征、肿瘤微环境（TME）、肿瘤突变负担（TMB）、微卫星不稳定性（MSI）、免疫检查点基因和药物敏感性之间的潜在关联在癌症基因组图谱（TCGA）肿瘤中。此外，在一些确证性队列（GSE111636、GSE78220、GSE67501、GSE176307、IMvigor210 和目前正在进行的 TRUCE01 临床研究中的 mRNA 测序数据）中研究了 BMPs 表达与免疫治疗效果的关联，并通过基因集富集分析（GSEA）探索了 BMPs 在膀胱癌（BCa）中的生物学功能和潜在信号通路。最后，通过 BMPs 在 BCa 中的表达、拷贝数或体细胞突变进行免疫浸润分析，并通过逆转录定量 PCR 和 Western blot 验证表达水平，以及 BMP8A 的体外功能实验。
研究结果表明，BMPs 的表达与 TCGA 肿瘤的预后、临床病理特征、突变、TME、TMB、MSI 和免疫检查点基因有关。抗癌药物敏感性分析表明，BMPs 与各种药物敏感性有关。此外，还发现某些 BMP 家族成员的表达水平与免疫治疗的客观反应有关。通过 GSEA，我们发现了多个与免疫相关的功能和途径被富集。BCa 的免疫浸润分析也显示了 BMPs 拷贝数变化、突变状态和不同免疫细胞浸润水平之间的显著相关性。此外，差异表达验证和体外表型实验表明，BMP8A 显著促进了 BCa 细胞的增殖、迁移和侵袭。
目前的结果证实了 BMPs 的表达和基因组改变在多种癌症的预后和治疗中的重要性，并表明 BMPs 可能对 BCa 很重要，并可能作为免疫治疗的生物标志物。
