Reddy P Sreekanth, Umesh Srikantha, Thota Balaram, Tandon Ashwani, Pandey Paritosh, Hegde A S, Balasubramaniam Anandh, Chandramouli B A, Santosh Vani, Rao M R S, Kondaiah Paturu, Somasundaram Kumaravel
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India.
Cancer Biol Ther. 2008 May;7(5):663-8. doi: 10.4161/cbt.7.5.5663.
Malignant astrocytomas comprise anaplastic astrocytoma (AA; grade III) and Glioblastoma (GBM; grade IV). GBM is the most malignant with a median survival of 10-12 months in patients. Using cDNA microarray based expression profiling of different grades of astrocytomas, we identified several fold increased levels of PBEF1 transcripts in GBM samples. Pre-B-cell colony enhancing factor 1 gene (PBEF1) encodes Nicotinamide phosphoribosyltransferase (NAmPRTase), which catalyses the rate limiting step in the salvage pathway of NAD metabolism in mammalian cells. Further validation using real time RT-qPCR on an independent set of tumor samples (n=91) and normal brain samples (n=9), GBM specific higher expression of PBEF1 was confirmed. Immunohistochemical staining for PBEF1 on a subset of the above samples largely reinforced our finding. We carried out ELISA analysis on serum samples of astrocytoma patients to determine whether this protein levels would correlate with the presence of tumor and tumor grade. PBEF1 serum levels were substantially elevated in many of the AA and GBM patients. Statistical analysis of these data indicates that in patients with astrocytoma, serum PBEF1 levels correlate with tumor grade and is highest in GBM. Immunohistochemical analysis of an independent set of 51 retrospective GBM cases with known survival data revealed that PBEF1 expression in the tumor tissue along with its co-expression with p53 was associated with poor survival. Thus, we have identified PBEF1 as a potential malignant astrocytoma serum marker and prognostic indicator among GBMs.
恶性星形细胞瘤包括间变性星形细胞瘤（AA；III级）和胶质母细胞瘤（GBM；IV级）。GBM是最恶性的，患者的中位生存期为10 - 12个月。通过基于cDNA微阵列的不同级别星形细胞瘤表达谱分析，我们发现在GBM样本中PBEF1转录本水平增加了数倍。前B细胞集落增强因子1基因（PBEF1）编码烟酰胺磷酸核糖基转移酶（NAmPRTase），它催化哺乳动物细胞中NAD代谢补救途径的限速步骤。使用实时RT-qPCR对另一组独立的肿瘤样本（n = 91）和正常脑样本（n = 9）进行进一步验证，证实了GBM中PBEF1的特异性高表达。对上述部分样本进行PBEF1免疫组化染色在很大程度上强化了我们的发现。我们对星形细胞瘤患者的血清样本进行ELISA分析，以确定该蛋白水平是否与肿瘤的存在和肿瘤级别相关。许多AA和GBM患者的PBEF1血清水平显著升高。对这些数据的统计分析表明，在星形细胞瘤患者中，血清PBEF1水平与肿瘤级别相关，在GBM中最高。对一组具有已知生存数据的51例回顾性GBM病例进行免疫组化分析发现，肿瘤组织中PBEF1的表达及其与p53的共表达与不良生存相关。因此，我们已将PBEF1确定为GBM中潜在的恶性星形细胞瘤血清标志物和预后指标。
