Department of Otorhinolaryngology Head and Neck Surgery, Xijing Hospital, The Air Force Military Medical University, Xi'an, China.
Department of Otorhinolaryngology Head and Neck Surgery, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Cell Commun Signal. 2024 Apr 12;22(1):227. doi: 10.1186/s12964-024-01605-x.
Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumors of the head and neck. Vasculogenic mimicry (VM) is crucial for tumor growth and metastasis and refers to the formation of fluid channels by invasive tumor cells rather than endothelial cells. However, the regulatory mechanisms underlying VM during the malignant progression of LSCC remain largely unknown.
Gene expression and clinical data for LSCC were obtained from the TCGA and Gene GEO (GSE27020) databases. A risk prediction model associated with VM was established using LASSO and Cox regression analyses. Based on their risk scores, patients with LSCC were categorized into high- and low-risk groups. The disparities in immune infiltration, tumor mutational burden (TMB), and functional enrichment between these two groups were examined. The core genes in LSCC were identified using the machine learning (SVM-RFE) and WGCNA algorithms. Subsequently, the involvement of bone morphogenetic protein 2 (BMP2) in VM and metastasis was investigated both in vitro and in vivo. To elucidate the downstream signaling pathways regulated by BMP2, western blotting was performed. Additionally, ChIP experiments were employed to identify the key transcription factors responsible for modulating the expression of BMP2.
We established a new precise prognostic model for LSCC related to VM based on three genes: BMP2, EPO, and AGPS. The ROC curves from both TCGA and GSE27020 validation cohorts demonstrated precision survival prediction capabilities, with the nomogram showing some net clinical benefit. Multiple algorithm analyses indicated BMP2 as a potential core gene. Further experiments suggested that BMP2 promotes VM and metastasis in LSCC. The malignant progression of LSCC is promoted by BMP2 via the activation of the PI3K-AKT signaling pathway, with the high expression of BMP2 in LSCC resulting from its transcriptional activation by runt-related transcription factor 1 (RUNX1).
BMP2 predicts poor prognosis in LSCC, promotes LSCC VM and metastasis through the PI3K-AKT signaling pathway, and is transcriptionally regulated by RUNX1. BMP2 may be a novel, precise, diagnostic, and therapeutic biomarker of LSCC.
喉鳞状细胞癌（LSCC）是头颈部最常见的恶性肿瘤之一。血管生成拟态（VM）对于肿瘤的生长和转移至关重要，它是指浸润性肿瘤细胞而不是内皮细胞形成的液体通道。然而，LSCC 恶性进展过程中 VM 的调控机制在很大程度上仍然未知。
从 TCGA 和基因 GEO（GSE27020）数据库中获取 LSCC 的基因表达和临床数据。使用 LASSO 和 Cox 回归分析建立与 VM 相关的风险预测模型。根据风险评分，将 LSCC 患者分为高风险组和低风险组。检测两组之间的免疫浸润、肿瘤突变负担（TMB）和功能富集的差异。使用机器学习（SVM-RFE）和 WGCNA 算法识别 LSCC 的核心基因。随后，在体外和体内研究骨形态发生蛋白 2（BMP2）在 VM 和转移中的作用。通过 Western blot 检测 BMP2 调节的下游信号通路。此外，还进行了 ChIP 实验以鉴定调节 BMP2 表达的关键转录因子。
我们基于三个基因（BMP2、EPO 和 AGPS）建立了一个新的、与 VM 相关的 LSCC 精确预后模型。来自 TCGA 和 GSE27020 验证队列的 ROC 曲线均显示出精确的生存预测能力，列线图显示出一定的净临床获益。多种算法分析表明 BMP2 是一个潜在的核心基因。进一步的实验表明，BMP2 促进 LSCC 的 VM 和转移。BMP2 通过激活 PI3K-AKT 信号通路促进 LSCC 的恶性进展，LSCC 中 BMP2 的高表达是由 runt 相关转录因子 1（RUNX1）转录激活引起的。
BMP2 预测 LSCC 的预后不良，通过 PI3K-AKT 信号通路促进 LSCC 的 VM 和转移，并受 RUNX1 的转录调控。BMP2 可能是 LSCC 的一种新的、精确的、诊断和治疗生物标志物。
