103P - Microsomal triglyceride transfer protein as a prognostic and therapeutic marker for brain cancer

Background

Glioblastoma multiforme (GBM) is the common malignant brain cancer and has poor prognosis despite development of modern medicine. The lipid metabolism is known to be correlated to cancer development and progression. Microsomal Triglyceride Transfer Protein (MTTP) is a molecule to lower lipids and its inhibitor, lomitapide, is involved in the improvement of hyperlipidemia. However, whether the altered expression of MTTP affects the development and prognosis of GBM is not identified.

Methods

Data for patients with brain cancer were prepared from The Cancer Genome Atlas (TCGA) database. Using t test or Mann-Whitney U test, datasets were compared to the expression of MTTP in normal and brain cancer tissues. The log-rank test and multivariable Cox proportional hazard regression were performed to assess if MTTP significantly affects the prognosis of patients with brain malignant tumor.

Results

MTTP expression was significantly higher in brain cancer than that in normal and the expression of MTTP in GBM was significantly higher than that in LGG. Moreover, the expression level of MTTP was significantly correlated with and cancer stage. MTTP expression was significantly increased in the IDH-WT than in the IDH mutant. Overall Survival (OS) of MTTP high and low expression groups was estimated 36.82 ± 6.612 and 75.02 ± 8.096, respectively (p < 0.001). Similar to this result, high MTTP expression had a poorer survival than low MTTP expression in LGG and GBM, respectively. In addition, brain cancer patients with older age and high MTTP expression had a significantly poor survival (median OS: 12.56 ± 0.876 months, p < 0.001).

Conclusions

The expression of MTTP was higher in brain cancer than in normal tissues. In addition, its expression was correlated to the age and stage of brain cancer patients. This results suggest that the function of MTTP may depend on the cancer type. The OS, PFS, and DSS of patients with high MTTP expression showed shorter than those with low MTTP expression. These results suggest that MTTP is a prognostic indicator in brain cancer. Taken together, our study will provide a framework for investigating the molecular mechanism of brain cancer development and progression and the additional use of lomitapide for GBM treatment.

Clinical trial identification

Editorial acknowledgement

The authors would like to acknowledge The Cancer Genome Atlas database and the GEO database.

Legal entity responsible for the study

The authors.

Funding

This study was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (NRF-2022R1F1A107476911; RJK) and Research Institue for Convergence of biomedical science and technology, Pusan National University Yangsan Hospital (30-2023-005).

Disclosure

All authors have declared no conflicts of interest.