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Bone morphogenetic protein 5 as a potential diagnostic and prognostic biomarker in lung adenocarcinoma
Caiping Tian1, Xiao Jing2, Hongyu Luo1
1Department of Medical Molecular Biology Research Center, Gansu Provincial Academic Institute for Medical Research, Lanzhou, China.
Background:
It is reported that bone morphogenetic protein 5 (BMP5) exerts a significant function in the pathogenesis of cancers. However, the role of BMP5 in lung adenocarcinoma (LUAD) is unclear. Thus, this study was conducted to excavate the diagnostic and prognostic significance of BMP5 in LUAD.
Methods:
The expression level and prognostic significance of BMP5 were analyzed in The Cancer Genome Atlas (TCGA) pan-cancer dataset of LUAD, followed by Gene Set Enrichment Analysis (GSEA) analysis. Correlation analysis between BMP5 and immune cell infiltration, immune checkpoints, and tumor mutation burden (TMB) were performed. The expression level, diagnostic and prognostic significances of BMP5 were confirmed in LUAD with Gene Expression Omnibus (GEO) datasets. The relationship between BMP5 expression and clinicopathological features of LUAD patients was analyzed, as well as BMP5-associated drugs for LUAD treatments. Lastly, in vitro experiments were carried out to evaluate the function of BMP5 in LUAD.
Results:
BMP5 was aberrantly expressed in most cancer types and showed prognostic predictive value and involved in energy-related pathways in most cancer types. BMP5 was significantly associated with immune checkpoint genes, immune activators, immunity inhibitors, immune cells, immunoscore, TMB and microsatellite instability (MSI) in most cancer types. Low expression of BMP5 was significantly associated with poor prognosis of LUAD patients, and BMP5 could accurately predict the prognosis of LUAD. In addition, BMP5 was strongly related to various clinicopathological parameters and immune cells of LUAD. The half maximal inhibitory concentration (IC50) values of axitinib, gefitinib and lapatinib were significantly increased in BMP5 high-expression group, while the IC50 of Olaparib was markedly decreased. In vitro experiments uncovered that BMP5 could inhibit tumorigenesis of LUAD.
Conclusions:
BMP5 is a valuable diagnostic and prognostic biomarker in LUAD. BMP5 might inhibit tumorigenesis of LUAD by targeting cell cycle pathway. Axitinib, gefitinib, lapatinib, and olaparib might be used for LUAD treatment by targeting BMP5.
