engleski

Integrative analysis of tumor suppressor CHUK in diffuse gliomas of the brain

Diffuse gliomas are primary brain tumors with aggressive biological behavior, poor prognosis, and lack of effective treatment methods. Although inhibitor of nuclear factor kappa-B kinase subunit alpha (IKK-α) plays an important role through NF- κB and AKT signaling in different types of cancer, the importance of this serin kinase in diffuse glioma is still unknown. Using the cBioPortal (https://www.cbioportal.org/) platform for large- scale analysis, 751 samples (62 diffuse astrocytomas, 129 anaplastic astrocytomas, and 560 glioblastomas) revealed changes in copy number aberrations(CNA), methylation, and mRNA expression of CHUK gene that encodes for IKK-α. CNA of CHUK were found in 75% of total samples and 99% of them were hemizygous deletions. The highest number of hemizygous deletions had glioblastomas with alterations in 88% of samples. Spearman’s test showed a statistically significant correlation between linear CNA data and tumor grade (r=-0.511 ; p<0.001). Likewise, a significant positive correlation was observed between CHUK methylation and tumor grade (Spearman’s r=0.796, p<0.001) as well as a negative correlation between mRNA expression and tumor grade (Spearman’s r=-0.351, p<0.001). These results suggest that hemizygous deletions and gene methylation inactivate this tumor suppressor during diffuse glioma progression to higher grades. The log-rank test showed higher, both overall and disease-free survival in diffuse glioma without CHUK deletions (p<0.001). These results demonstrate the important role of CHUK in the progression of diffuse glioma as well as the specific molecular signature of each pathohistological type examined in this study. Also, we suggest that CHUK CNA status could be used as a molecular marker for prognosis and potential treatment target in patients with diffuse glioma.

astrocytoma ; glioma ; glioblastoma ; I-kappa B kinase ; NF-kappa B

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