骨形成蛋白及其受体在肺腺癌中的异常表达及预后意义。
Abnormal Expression and Prognostic Significance of Bone Morphogenetic Proteins and Their Receptors in Lung Adenocarcinoma.
机构信息
Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 Zhejiang, China.
The Interventional Pulmonary Key Laboratory of Zhejiang Province, Wenzhou, 325000 Zhejiang, China.
出版信息
Biomed Res Int. 2021 May 7;2021:6663990. doi: 10.1155/2021/6663990. eCollection 2021.
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.
背景
肺腺癌（LUAD）是最具威胁生命的恶性肿瘤之一。骨形态发生蛋白（BMP）/BMP 受体的关键作用揭示了探索 LUAD 中 BMP 蛋白相关预后预测因子的重要性。
方法
检测 LUAD 和正常肺组织中 BMPs/BMP 受体的 mRNA 表达。进行基因本体论和京都基因与基因组百科全书通路分析，并通过 Kaplan-Meier Plotter 评估预后值。进行单因素和多因素 Cox 回归分析，以确定 BMPs/BMP 受体的 mRNA 表达与总生存期（OS）之间的相关性。采用受试者工作特征（ROC）曲线评估预后模型的预测能力。然后，在 GEO 队列中验证该预后模型。此外，建立了包含该预后模型的列线图。
结果
与正常肺组织相比，LUAD 组织中 BMP2/5/6/R2、ACVRL1 和 TGFBR2/3 的 mRNA 表达较低。BMP2/4/5/R1A/R2、ACVR1/2A/L1 和 TGFBR1/3 的高表达与更好的 OS 相关，而 BMP7 和 ACVR1C/2B 与更差的 OS 相关。通过单因素和多因素 Cox 回归分析筛选出 3 个基因（BMP5、BMP7 和 ACVR2A），用于在 TCGA 中构建预后模型。与高风险评分的 LUAD 患者相比，低风险评分的 LUAD 患者的生存率显著提高。ROC 曲线证实了该预后模型的良好性能，然后在 GSE31210 数据集进行了验证。构建了一个列线图（AUCs＞0.7）。进一步评估了关键基因，包括基因集富集分析和免疫细胞浸润。
结论
BMP5、BMP7 和 ACVR2A 是 LUAD 的潜在治疗靶点。三基因预后模型和列线图是预测 LUAD 患者 OS 的可靠工具。
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