Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, China.
Curr Med Sci. 2024 Apr;44(2):309-327. doi: 10.1007/s11596-023-2806-6. Epub 2024 Mar 22.
Lung squamous cell carcinoma (LUSC) is associated with a low survival rate. Evidence suggests that bone morphogenetic proteins (BMPs) and their receptors (BMPRs) play crucial roles in tumorigenesis and progression. However, a comprehensive analysis of their role in LUSC is lacking. Our study aimed to explore the relationship between BMPs/BMPRs expression levels and the tumorigenesis and prognosis of LUSC.
The "R/Limma" package was utilized to analyze the differential expression characteristics of BMPs/BMPRs in LUSC, using data from TCGA, GTEx, and GEO databases. Concurrently, the "survminer" packages were employed to investigate their prognostic value and correlation with clinical features in LUSC. The core gene associated with LUSC progression was further explored through weighted gene correlation network analysis (WGCNA). LASSO analysis was conducted to construct a prognostic risk model for LUSC. Clinical specimens were examined by immunohistochemical analysis to confirm the diagnostic value in LUSC. Furthermore, based on the tumor immune estimation resource database and tumor-immune system interaction database, the role of the core gene in the tumor microenvironment of LUSC was explored.
GDF10 had a significant correlation only with the pathological T stage of LUSC, and the protein expression level of GDF10 decreased with the tumorigenesis of LUSC. A prognostic risk model was constructed with GDF10 as the core gene and 5 hub genes (HRASLS, HIST1H2BH, FLRT3, CHEK2, and ALPL) for LUSC. GDF10 showed a significant positive correlation with immune cell infiltration and immune checkpoint expression.
GDF10 might serve as a diagnostic biomarker reflecting the tumorigenesis of LUSC and regulating the tumor immune microenvironment to guide more effective treatment for LUSC.
肺鳞状细胞癌（LUSC）的存活率较低。有证据表明，骨形态发生蛋白（BMPs）及其受体（BMPRs）在肿瘤发生和进展中起着至关重要的作用。然而，它们在 LUSC 中的作用尚缺乏全面分析。本研究旨在探讨 BMPs/BMPRs 表达水平与 LUSC 发生和预后的关系。
使用 TCGA、GTEx 和 GEO 数据库中的数据，通过“R/Limma”包分析 LUSC 中 BMPs/BMPRs 的差异表达特征。同时，使用“survminer”包研究其在 LUSC 中的预后价值及其与临床特征的相关性。通过加权基因相关网络分析（WGCNA）进一步探讨与 LUSC 进展相关的核心基因。进行 LASSO 分析以构建 LUSC 的预后风险模型。通过免疫组织化学分析检查临床标本，以验证其在 LUSC 中的诊断价值。此外，基于肿瘤免疫估计资源数据库和肿瘤-免疫系统相互作用数据库，探讨核心基因在 LUSC 肿瘤微环境中的作用。
GDF10 仅与 LUSC 的病理 T 分期有显著相关性，且 GDF10 蛋白表达水平随 LUSC 的发生而降低。以 GDF10 为核心基因，构建了一个包含 5 个关键基因（HRASLS、HIST1H2BH、FLRT3、CHEK2 和 ALPL）的 LUSC 预后风险模型。GDF10 与免疫细胞浸润和免疫检查点表达呈显著正相关。
GDF10 可能作为反映 LUSC 发生的诊断生物标志物，并调节肿瘤免疫微环境，以指导更有效的 LUSC 治疗。
