Prognostic role and tumor-suppressive effects of CADM family members and the potential molecular mechanisms of CADM1 in neuroblastoma.

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.