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.