Han Yan-Long, Luo Dan, Habaxi Kakeng, Tayierjiang Julaiti, Zhao Wei, Wang Wei, Aikebaier Wumaierjiang, Wang Li
Department of Bone and Joint Surgery Center, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.
Department of Respiratory and Critical Care Medicine, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.
Front Oncol. 2022 Feb 24;12:813809. doi: 10.3389/fonc.2022.813809. eCollection 2022.
Osteosarcoma is the most common skeletal malignancy and is the second leading cause of cancer death in adolescents. Its highly aggressive nature and high propensity to metastasize lead to an extremely poor prognosis for patients with osteosarcoma. Therefore, finding a suitable treatment has become a matter of urgency. In this study, we first divided the samples into metastatic and non-metastatic groups using the Target database and obtained 1136 differentially expressed genes (DEGs) using differential analysis. A PPI network was constructed to analyze the network of action relationships among DEGs, and the top 10 genes were derived using the MCC algorithm in Cytoscape software. A risk scoring system for 10 key genes was constructed using the LASSO-COX prognostic risk model, and genes associated with osteosarcoma prognosis were screened based on multifactorial COX. COL5A2 gene was highly expressed in metastatic osteosarcoma and led to a poor prognosis. Furthermore, qRT-PCR and immunofluorescence assays confirmed the high expression of COL5A2 in human osteosarcoma cells. CCK-8 assay and scratch WB was used to determine whether the downregulation of COL5A2 expression inhibits the TGF-β signaling and Wnt/β-Catenin signaling pathways. In this study, we screened COL5A2 for prognostic relevance to osteosarcoma through bioinformatics analysis and demonstrated that COL5A2 inhibited osteosarcoma invasion and metastasis by suppressing the TGF-β signaling and Wnt/β-Catenin signaling pathways.
骨肉瘤是最常见的骨骼恶性肿瘤,是青少年癌症死亡的第二大主要原因。其高度侵袭性和高转移倾向导致骨肉瘤患者的预后极差。因此,找到合适的治疗方法已成为当务之急。在本研究中,我们首先使用Target数据库将样本分为转移组和非转移组,并通过差异分析获得了1136个差异表达基因(DEG)。构建了一个蛋白质-蛋白质相互作用(PPI)网络来分析DEG之间的作用关系网络,并使用Cytoscape软件中的MCC算法得出前10个基因。使用LASSO-COX预后风险模型构建了10个关键基因的风险评分系统,并基于多因素COX筛选了与骨肉瘤预后相关的基因。COL5A2基因在转移性骨肉瘤中高表达,并导致预后不良。此外,qRT-PCR和免疫荧光测定证实了COL5A2在人骨肉瘤细胞中的高表达。使用CCK-8测定法和划痕实验来确定COL5A2表达的下调是否抑制TGF-β信号通路和Wnt/β-连环蛋白信号通路。在本研究中,我们通过生物信息学分析筛选了与骨肉瘤预后相关的COL5A2,并证明COL5A2通过抑制TGF-β信号通路和Wnt/β-连环蛋白信号通路来抑制骨肉瘤的侵袭和转移。