Gene Expression Analysis of anEGFRIndirectly Related Pathway IdentifiedPTENandMMP9as Reliable Diagnostic Markers for Human Glial Tumor Specimens

[摘要] In this study the mRNA levels of fiveEGFRindirectly related genes,EGFR,HB-EGF,ADAM17,PTEN, andMMP9, have been assessed by Real-time PCR in a panel of 37 glioblastoma multiforme specimens and in 5 normal brain samples; as a result, in glioblastoma,ADAM17andPTENexpression was significantly lower than in normal brain samples, and, in particular, a statistically significant inverse correlation was found betweenPTENandMMP9mRNA levels. To verify if this correlation was conserved in gliomas,PTENandMMP9expression was further investigated in an additional panel of 16 anaplastic astrocytoma specimens and, in parallel, in different human normal and astrocytic tumor cell lines. In anaplastic astrocytomasPTENexpression was significantly higher than in glioblastoma multiforme, but no significant correlation was found betweenPTENandMMP9expression.PTENandMMP9mRNA levels were also employed to identify subgroups of specimens within the different glioma malignancy grades and to define a gene expression-based diagnostic classification scheme. In conclusion, this gene expression survey highlighted that the combined measurement ofPTENandMMP9transcripts might represent a novel reliable tool for the differential diagnosis of high-grade gliomas, and it also suggested a functional link involving these genes in glial tumors.

[学科分类] 基础医学