Implications of the heterogeneous gene expression traits in recurrent glioblastoma

ABSTRACT: Glioblastoma multiforme (GBM) is the most aggressive and frequent primary brain tumor with dismal prognosis which might be due to the resistance to the current standard chemotherapeutic regimens and high recurrence rate even after total resection of GBM mass. Here, to gain the mechanistic insights on the altered phenotypic acquisition of recurrent tumors compared to the corresponding primary tumors, we performed gene expression profiling on the 43 cases of GBM tumors including 15 paired recurrent and primary GBMs. Unsupervised and consensus clustering analyses revealed two subtypes of G1 and G2, which were enriched with proliferation, and neuron-like gene expression traits, respectively. Most of the primary tumors were classified into G1, while the recurrent tumors were classified into both G1 and G2 groups. The gene expression of recurrent GBMs in G2 group have changed from proliferation type to neuron-like type, while the other recurrent GBMs in the G1 group showed no significant subtype change. In addition, we observed that the recurrent tumors in G1 subtype were characterized with the expression of stemness-related genes and DNA-repair genes. Of the G1 subtype classifier genes, AURKA/B and HOX genes were identified as key hub regulators. On the other hand, the recurrent G2 tumors have acquired the expression of MGMT but suppression of MSH6 gene, which may lead to TMZ resistance. The consistency of these findings could be validated with independent data sets. In summary, our molecular classification of recurrent GBMs could suggest that the differential mechanisms of drug resistance be involved in the tumor recurrence. Targeting the subtype-specific mechanisms might be a beneficial strategy for the treatment of recurrent GBMs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE62153 | GEO | 2015/10/20

SECONDARY ACCESSION(S): PRJNA263295

REPOSITORIES: GEO