MYH gene family associated with high mortality risk in elderly glioma patients with frontal lobe primary site.

INTRODUCTION: Mortality risk of glioma varies significantly by tumor primary site. This study aims to explore the mechanisms underlying such survival differences. METHODS: This study used the SEER 17 database, which enrolled 8426 patients with Adult-type Diffuse Gliomas. We analyzed mortality risk in glioma patients with different primary sites via the Kaplan-Meier method, Cox regression, and propensity score matching. Based on transcriptome data from the CPTAC-GBM and TCGA-LGG cohorts, we identified lobe-specific differentially expressed genes in age-stratified cohorts (young group: ≤60 years; elderly group: >60 years). We then performed functional enrichment analysis and interaction network analysis for the differentially expressed genes. Finally, we explored the regulatory mechanisms through in silico gene knockout and co-expression network perturbation analysis. RESULTS: Multivariate Cox regression showed that patients with the frontal lobe as the primary site had significantly higher mortality risk than those with tumors in other brain lobes (P < 0.001). This finding was validated after propensity score matching. Subgroup analysis and interaction analysis revealed a significant interaction between tumor primary site and patient age group (P = 0.0013). Specifically, elderly patients (>60 years) with Adult-type Diffuse Gliomas in the frontal lobe had higher mortality than patients with tumors in other primary sites. Transcriptome analyses based on the two cohorts confirmed the critical role of the MYH gene family in elderly patients with frontal lobe glioma. Virtual gene knockout and co-expression network perturbation analysis indicated that the MYH gene family may affect patient survival by regulating tumor-associated genes. CONCLUSIONS: Mortality risk interacts with age in glioma patients with different primary sites. The elderly patients with frontal lobe glioma have higher mortality risk. This elevated risk is potentially associated with the high expression of MYH gene family members in frontal lobe tumors. These genes may contribute to the dysregulation of related genes and pathways involved in tumor proliferation and invasion, which could represent a potential mechanism underlying the observed mortality difference.