Glioblastoma multiforme (GBM) is a highly aggressive malignancy and represents the most common brain tumor in adults. To better understand its biology for new and effective therapies, we examined the role of GDP-mannose pyrophosphorylase B (GMPPB), a key unit of the GDP-mannose pyrophosphorylase (GDP-MP) that catalyzes the formation of GDP-mannose. Impaired GMPPB function will reduce the amount of GDP-mannose available for O-mannosylation. Abnormal O-mannosylation of alpha dystroglycan (α-DG) has been reported to be involved in cancer metastasis and arenavirus entry. Here, we found that GMPPB is highly expressed in a panel of GBM cell lines and clinical samples and that expression of GMPPB is positively correlated with the WHO grade of gliomas. Additionally, expression of GMPPB was negatively correlated with the prognosis of GBM patients. We demonstrate that silencing GMPPB inhibits the proliferation, migration, and invasion of GBM cells both in vitro and in vivo and that overexpression of GMPPB exhibits the opposite effects. Consequently, targeting GMPPB in GBM cells results in impaired GBM tumor growth and invasion. Finally, we identify that the Hippo/MMP3 axis is essential for GMPPB-promoted GBM aggressiveness. These findings indicate that GMPPB represents a potential novel target for GBM treatment.

Background/Objectives: The efficacy and time-dependent pattern of consolidation immunotherapy after induction chemoimmunotherapy and radiotherapy remain unclear in unresectable stage III non-small cell lung cancer (NSCLC). This study evaluated the efficacy and temporal pattern of consolidation immunotherapy in this population. Methods: This dual-center retrospective cohort study included patients with unresectable stage III NSCLC who achieved disease control after induction chemoimmunotherapy followed by definitive radiotherapy. To reduce potential immortal time bias, only patients who remained alive and progression-free within 2 months after radiotherapy were included. Patients were grouped according to receipt of consolidation immunotherapy. Survival outcomes were analyzed using stabilized inverse probability of treatment weighting, multivariable Cox regression, sequential landmark Cox analysis, and landmark restricted mean survival time analysis. Results: Among 170 eligible patients, 65 received consolidation immunotherapy and 105 did not. After a median follow-up of 33 months, consolidation immunotherapy was associated with longer PFS (hazard ratio [HR]: 0.52, 95% confidence interval [CI]: 0.35–0.78, p = 0.001) and OS (HR: 0.35, 95% CI: 0.18–0.65, p < 0.001). These benefits remained significant after weighting, and multivariable analysis identified consolidation immunotherapy as an independent predictor of improved PFS. Exploratory sequential landmark Cox and restricted mean survival time analyses suggested that the survival benefit was more evident during the early treatment period, particularly around 8–10 months. Conclusions: Consolidation immunotherapy was associated with improved survival, and its benefit appeared more evident during the early treatment period, particularly around 8–10 months. The optimal treatment duration requires further prospective validation.