Gene Expression Analysis of an EGFR Indirectly Related Pathway Identified PTEN and MMP9 as Reliable Diagnostic Markers for Human Glial Tumor Specimens

Abstract

In this study the mRNA levels of five EGFR indirectly related genes, EGFR, HB-EGF, ADAM17, PTEN, and MMP9, 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, ADAM17 and PTEN expression was significantly lower than in normal brain samples, and, in particular, a statistically significant inverse correlation was found between PTEN and MMP9 mRNA levels. To verify if this correlation was conserved in gliomas, PTEN and MMP9 expression 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 astrocytomas PTEN expression was significantly higher than in glioblastoma multiforme, but no significant correlation was found between PTEN and MMP9 expression. PTEN and MMP9 mRNA 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 of PTEN and MMP9 transcripts 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.

miR-204-5p acts as a tumor suppressor by targeting matrix metalloproteinases-9 and B-cell lymphoma-2 in malignant melanoma

“…MMP9, a member of the MMP family, degrades these collagens, thereby expediting and facilitating cancer cell invasion and metastasis 30. MMP9 is overexpressed in various human cancer types 31,32. A large number of studies have verified that many oncogenes and tumor suppressor genes influence cancer progression through regulation of BCL2 and MMP9, including melanoma 33,34.…”

Glioblastoma Cell Enrichment Is Critical for Analysis of Phosphorylated Drug Targets and Proteomic–Genomic Correlations

“…This indicates that for largely tumor cell-specific proteins, the analysis of large numbers of samples may overcome the observed increased patient-to-patient variation following whole-tissue lysis. In contrast to EGFR, PTEN is highly expressed in normal brain (25,30). In fact, loss of PTEN copy number is frequently found in glioblastoma multiforme (15) and is under intense investigation as a companion diagnostic marker for PI3K/AKT/mTOR targeting therapies.…”

Glioma Cell Biology

“…Ambiguous data Decreased expression reported by Comincini et al (2009), increased according to TCGA data; mediates hypoxia-induced glioma invasiveness (Zheng et al 2007); may contribute to stemness maintenance through the Notch signaling ); promotes the malignant phenotype of glioma cells ); introduction into astrocytes induced a neoplastic phenotype by deregulating EGFR signaling ); involved in the impaired immune recognition of glioma stem cells (Wolpert et al 2014). …”