Background: The bone morphogenetic family proteins (BMP) are phytogenetically conserved proteins, which are essential for embryonic development. The key regulatory subunit, the bone morphogenetic protein 4 (BMP4), is overexpressed and associated with tumor metastasis in a variety of cancers. However, the prognostic and molecular features of gliomas with BMP4 expression is still unclear. Methods: We obtained whole genome mRNA expression microarray data of 220 glioma samples of all grades from Chinese Glioma Genome Atlas (CGGA) database (http://www.cgga.org.cn) as discovery set. Of the 123 high-grade gliomas in this set, 33 Grade III tumors and 88 GBMs were analyzed by Kaplan-Meier method. Immunohistochemistry was used for validating the expression of BMP4 in another 77 glioma samples. Three additional datasets were obtained as validation sets. Gene ontology (GO) analysis and gene set variation analysis (GSVA) were used for functional annotation of BMP4. Results: In the discovery set, BMP4 overexpression was significantly associated with low grade as well as the lower mortality of high-grade gliomas in survival analysis (log-rank, p<0.05 in GBM patients and p<0.01 in anaplastic gliomas, respectively). BMP4 also showed a Proneural subtype, G1 subtype and Isocitrate Dehydrogenase 1 (IDH1) mutation preference and cell development association. The results of validation 4 datasets showed similar findings. The overexpression of BMP4 was also detected in low grade gliomas compared to the high grade ones by immunohistochemistry (p<0.05, chi-square test). Conclusion: BMP4 expression was independently associated with grade and good prognosis in grade III and grade IV gliomas, suggesting BMP4 as a novel biomarker with potential important therapeutic implications.
基金:
National High Technology Research and Development ProgramNational High Technology Research and Development Program of China [2012AA02A508]; International Science and Technology Cooperation Program [2012DFA30470]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81201993]; National 973 programNational Basic Research Program of China [2011CB707804]
第一作者机构:[1]Capital Med Univ, Beijing Tiantan Hosp, Dept Neurosurg, Beijing 100050, Peoples R China;
通讯作者:
通讯机构:[1]Capital Med Univ, Beijing Tiantan Hosp, Dept Neurosurg, Beijing 100050, Peoples R China;
推荐引用方式(GB/T 7714):
Bao Zhaoshi,Zhang Chuanbao,Yan Wei,et al.BMP4, a strong better prognosis predictor, has a subtype preference and cell development association in gliomas[J].JOURNAL OF TRANSLATIONAL MEDICINE.2013,11(1):-.doi:10.1186/1479-5876-11-100.
APA:
Bao, Zhaoshi,Zhang, Chuanbao,Yan, Wei,Liu, Yanwei,Li, Mingyang...&Jiang, Tao.(2013).BMP4, a strong better prognosis predictor, has a subtype preference and cell development association in gliomas.JOURNAL OF TRANSLATIONAL MEDICINE,11,(1)
MLA:
Bao, Zhaoshi,et al."BMP4, a strong better prognosis predictor, has a subtype preference and cell development association in gliomas".JOURNAL OF TRANSLATIONAL MEDICINE 11..1(2013):-