Wang Yu, Zheng Lingling, Liu Jun, Zhang Mingyu, Kan Ying, Wang Wei, Yang Jigang
Department of Nuclear Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
Discov Oncol. 2025 May 1;16(1):648. doi: 10.1007/s12672-025-02350-4.
The exact role of cell adhesion molecule (CADM) family members in neuroblastoma is still being explored. Here we uncovered the survival association and the possible mechanisms of CADMs in neuroblastoma through comprehensive bioinformatic analyses. Then the results of CADM1 were verified in neuroblastoma cell lines.
CADMs expression was examined by cBioPortal and TARGET databases and verified in several GEO datasets. Kaplan-Meier plot, log-rank test, the ROC curve, and Cox regression analysis were utilized to assess the prognostic value of CADMs in neuroblastoma. Through functional enrichment analysis and interaction network construction, hub genes were screened to explore the molecular mechanism of CADMs in neuroblastoma. We tested the abilities of cell growth and migration in neuroblastoma cells when CADM1 was silenced and overexpressed respectively. We then used western blot to verify the phosphorylation levels of AKT/GSK-3β pathways.
The expression of CADM1-4 was significantly down-regulated in neuroblastoma patients with unfavorable prognostic factors. Moreover, CADM1 and CADM3 increased the accuracy of classical clinical indicators for predicting survival rate. The top 10 KEGG pathways for CADMs and their co-expression genes were mainly enriched in the mitotic cell cycle and the process of chromosomal duplication. Furthermore, our study showed that CADM1 inhibited neuroblastoma cells proliferation, migration and the phosphorylation of GSK-3β.
Decreased expression of CADM1 and CADM3 was significantly associated with poor outcomes in neuroblastoma. CADM1 may suppress neuroblastoma cell proliferation and migration through regulating the phosphorylation of GSK-3β.
细胞粘附分子（CADM）家族成员在神经母细胞瘤中的确切作用仍在探索中。在此，我们通过全面的生物信息学分析揭示了CADM在神经母细胞瘤中的生存关联及可能机制。然后在神经母细胞瘤细胞系中验证了CADM1的结果。
通过cBioPortal和TARGET数据库检测CADM的表达，并在多个GEO数据集中进行验证。利用Kaplan-Meier曲线、对数秩检验、ROC曲线和Cox回归分析评估CADM在神经母细胞瘤中的预后价值。通过功能富集分析和相互作用网络构建，筛选枢纽基因以探索CADM在神经母细胞瘤中的分子机制。我们分别检测了CADM1沉默和过表达时神经母细胞瘤细胞的生长和迁移能力。然后用蛋白质免疫印迹法验证AKT/GSK-3β信号通路的磷酸化水平。
CADM1-4在具有不良预后因素的神经母细胞瘤患者中表达显著下调。此外，CADM1和CADM3提高了经典临床指标预测生存率的准确性。CADM及其共表达基因的前10个KEGG通路主要富集在有丝分裂细胞周期和染色体复制过程中。此外，我们的研究表明，CADM1抑制神经母细胞瘤细胞的增殖、迁移以及GSK-3β的磷酸化。
CADM1和CADM3表达降低与神经母细胞瘤的不良预后显著相关。CADM1可能通过调节GSK-3β的磷酸化来抑制神经母细胞瘤细胞的增殖和迁移。
