Holistic and network analysis of meningioma pathogenesis and malignancy.

Meningiomas, which originate from arachnoid cells and constitute the largest subgroup of all intracranial tumors, are generally benign, yet have the capacity to progress into a higher histological grade of malignancy associated with an increase in biological aggressivity and/or capacity to recur. To elucidate meningioma pathogenesis and malignancy, we applied a holistic and network approach analyzing cDNA and tissue microarray results. A potential pathway leading to meningioma angiogenesis, apoptosis and proliferation was evidenced as well as a regulatory network of the biomarkers including Ki-67, AR, CD34, P53, c-MYC, etc. which might support clinical research. In this potential pathway, ITGB1 could be the most important "superoncogene" playing a vital role in apoptosis and proliferation, while FOXO3A, MDM4 and MT3 are important to the malignancy process. Some genes are first reported that could explain why radiation induces meningioma and why more female than male patients are affected. Further, we present the hypothesis that HIV-Tat protein might have a close relationship with meningioma pathogenesis and malignancy.