Meng Fanyu, Zhou Xinshe, Zhao Zhi, Pei Lijia, Xia Weiguo
Department of Orthopedics, Lixin County People's Hospital, Bozhou, 236700, China.
Department of Orthopedics, the First Affiliated Hospital of Bengbu Medical University, Bengbu, 233000, China.
J Appl Genet. 2025 May;66(2):323-332. doi: 10.1007/s13353-024-00872-1. Epub 2024 May 30.
Osteosarcoma is a primary malignant bone tumor that affects children and young adults. Understanding the molecular mechanisms underlying osteosarcoma is critical to develop effective treatments. This study aimed to identify core genes and explore the role of intercellular communication in osteosarcoma. We used GSE87437 and GSE152048 dataset to conduct a weighted correlation network analysis (WGCNA) and identify co-expression modules. The enriched biological processes and cellular components of the genes in the steelblue module were analyzed. Next, we explored the expression, diagnostic value, correlation, and association with immune infiltrate of CCSER1 and LOC101929154. Finally, we utilized CIBERSORT algorithm to predict the infiltrated immune cells in osteosarcoma tissues. Our results identified 44 co-expression modules, and the steelblue module was mainly associated with axon development, axonogenesis, and innervation. CCSER1 and LOC101929154 were significantly upregulated in osteosarcoma tissues with poor response to preoperative chemotherapy. Moreover, the expressions of CCSER1 and LOC101929154 were positively correlated. The area under the receiver operating characteristic curve of CCSER1 and LOC101929154 was 0.800 and 0.773, respectively. The expression of CCSER1 was negatively correlated with follicular helper T cells and positively correlated with M0 macrophages, while LOC101929154 was negatively correlated with activated mast cells. Besides, CD4 memory-activated T cells were observed at lower levels in patients who responded well to chemotherapy. Our study identified core genes CCSER1 and LOC101929154 and provided insight into the intercellular communication profile in osteosarcoma. Our results suggested that targeting CCSER1, LOC101929154, and CD4 memory-activated T cells may be a promising strategy for the treatment of osteosarcoma.
骨肉瘤是一种影响儿童和年轻人的原发性恶性骨肿瘤。了解骨肉瘤潜在的分子机制对于开发有效的治疗方法至关重要。本研究旨在识别核心基因并探索细胞间通讯在骨肉瘤中的作用。我们使用GSE87437和GSE152048数据集进行加权相关网络分析（WGCNA）并识别共表达模块。分析了钢蓝色模块中基因的富集生物学过程和细胞成分。接下来，我们探究了CCSER1和LOC101929154的表达、诊断价值、相关性以及与免疫浸润的关联。最后，我们利用CIBERSORT算法预测骨肉瘤组织中浸润的免疫细胞。我们的结果识别出44个共表达模块，钢蓝色模块主要与轴突发育、轴突形成和神经支配相关。CCSER1和LOC101929154在对术前化疗反应不佳的骨肉瘤组织中显著上调。此外，CCSER1和LOC101929154的表达呈正相关。CCSER1和LOC101929154的受试者工作特征曲线下面积分别为0.800和0.773。CCSER1的表达与滤泡辅助性T细胞呈负相关，与M0巨噬细胞呈正相关，而LOC101929154与活化肥大细胞呈负相关。此外，化疗反应良好的患者中CD-4记忆活化T细胞水平较低。我们的研究识别出核心基因CCSER1和LOC101929154，并深入了解了骨肉瘤中的细胞间通讯概况。我们的结果表明，靶向CCSER1、LOC101929154和CD-4记忆活化T细胞可能是治疗骨肉瘤的一种有前景的策略。
