Abnormal Expression and Prognostic Significance of Bone Morphogenetic Proteins and Their Receptors in Lung Adenocarcinoma | Zendy

Zhixiao Xu | Zendy; Chengshui Chen | Zendy

Open Access

Abnormal Expression and Prognostic Significance of Bone Morphogenetic Proteins and Their Receptors in Lung Adenocarcinoma

Author(s) -

Zhixiao Xu,

Chengshui Chen

Publication year - 2021

Publication title -

biomed research international

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.772

H-Index - 126

eISSN - 2314-6141

pISSN - 2314-6133

DOI - 10.1155/2021/6663990

Subject(s) - bone morphogenetic protein , adenocarcinoma , receptor , lung , bone morphogenetic protein receptor , bone morphogenetic protein 2 , medicine , cancer research , biology , bone morphogenetic protein 7 , pathology , bioinformatics , genetics , gene , cancer , in vitro

Background Lung adenocarcinoma (LUAD) is one of the most life-threatening malignancies. The crucial role of bone morphogenetic protein (BMP)/BMP receptors reveals the significance of exploring BMP protein-related prognostic predictors in LUAD.Methods The mRNA expression of BMPs/BMP receptors was investigated in LUAD and normal lung tissues. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed, and the prognostic values were assessed by Kaplan-Meier Plotter. Univariate and multivariate Cox regression analyses were executed to ascertain the correlation between overall survival (OS) and the mRNA expression of BMPs/BMP receptors. The receiver operating characteristic (ROC) curves were implemented to evaluate the predictive power of the prognostic model. Then, the prognostic model was validated in the GEO cohort. Furthermore, a nomogram comprising the prognostic model was established.Results The mRNA expression of BMP2/5/6/R2, ACVRL1, and TGFBR2/3 was lower in LUAD tissues than in normal lung tissues. High expression of BMP2/4/5/R1A/R2, ACVR1/2A/L1, and TGFBR1/3 was associated with better OS, while BMP7 and ACVR1C/2B were associated with poorer OS. Three genes (BMP5, BMP7, and ACVR2A) were screened by univariate and multivariate Cox regression analyses to develop the prognostic model in TCGA. Significantly better survival was observed in LUAD patients with a low-risk score than those with a high-risk score. The ROC curves confirmed the good performance of the prognostic model, then, the prognostic model was validated in the GSE31210 dataset. A nomogram was constructed (AUCs>0.7). And hub genes were further evaluated, including gene set enrichment analysis and immune cell infiltration.Conclusions BMP5, BMP7, and ACVR2A are potential therapeutic targets in LUAD. The three-gene prognostic model and the nomogram are reliable tools for predicting the OS of LUAD patients.

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