gms | German Medical Science

Objective: Even though stereotactic radiosurgery and fractionated stereotactic radiotherapy are well-established treatment modalities for vestibular schwannoma (VS) patients, vestibular schwannoma tumor cells are relatively resistant to irradiation. The radioresistance is possibly due to their low proliferation rate or due to constitutive activation of signaling pathways. However, the molecular mechanisms associated with recurrent vestibular schwannoma growth following radiation therapy are still not well understood.

The objective of this study was to provide insight into the molecular biology of irradiated vestibular schwannoma through gene expression profiling and pathway analysis.

Method: RNA of snap-frozen tumor samples of 36 non-irradiated and 7 irradiated vestibular schwannomas was extracted for microarray gene expression analysis (HG-U219 Array Plate, Affymetrix^®). We utilized canonical pathway analysis (Ingenuity Pathway Analysis, IPA) to investigate pathways affected by irradiation.

Results: A total of 248 probe sets (121 genes were up- and 127 downregulated) showed significant difference based on the criteria of P value < 0.01 and absolute fold change ≥ 2. Most of the genes were involved in pathways of ErbB-Signaling and VEGF-Signaling. The ErbB molecules, ErbB2 and ErbB3, emerged as central nodes of pathway analysis and were significantly downregulated.

Conclusions: Using microarray technology we verified that ErbB-Signaling and its molecules ErbB2 and ErbB3 play a putative role in irradiated VS. As previously described, primary cultures of VS cells exhibit radioresistance after inhibition of ErbB2-Signaling. This pathway may hold important implications for current and future treatment modalities of irradiated VS.