BMP4, a new prognostic factor for glioma

BACKGROUND The expression status of bone morphogenetic protein 4 (BMP4) in gliomas is still unclear by now. We try to investigate the relationship between BMP4 expression and the biological behavior of gliomas in order to lay a foundation for the management of these tumors. METHODS A total of 630 patients with glioma were enrolled in the study from January 2002 to January 2008. The expression status of BMP4 in gliomas was evaluated by RT-PCR and immunohistochemistry. The relationships between BMP4 expression and clinicopathological parameters and between BMP4 expression and prognosis were also studied. RESULTS The expression of BMP4 in tumor tissues was significantly lower than that in the paracancer tissues at both mRNA and protein levels (P = 0.01 and 0.001, respectively). Univariate analysis showed that BMP4 expression was closely related to extent of resection, Ki-67 expression, and the WHO grade (P = 0.001, 0.001, and 0.001, respectively), but it was not related to age, sex, or the Karnofsky Performance Status (KPS) score (P = 0.099, 0.472, and 0.201, respectively). Finally, Ki-67 expression and the WHO grade were found to be related to BMP4 expression using logistic regression (P = 0.001 and 0.001, respectively). Interestingly, we found that the expression of BMP4 was significantly related to distant glioma metastasis. Cox regression analysis identified the KPS score, extent of resection, Ki-67 expression, WHO grade, and BMP4 expression as independent prognostic factors (P = 0.044, 0.010, 0.002, 0.001, and 0.001, respectively). CONCLUSIONS BMP4 is differentially expressed in glioma patients and is closely related to the biological behavior of gliomas. BMP4 expression was found to be a strong predictor of distant metastasis and postoperative prognosis.