Alterations of the tumor microenvironment (TME) by exploratory gene expression analysis in recurrent glioblastoma following apatinib in combination with temozolomide

Apatinib in combination with temozolomide (TMZ) has achieved reasonable clinical efficacy in the treatment of recurrent glioblastoma (rGBM), however, there are currently no clear biomarkers related to clinical efficacy or prognosis. Our retrospective study was to investigate tumor microenvironment (TME) features at the gene expression level that are associated with response and long survival benefit of rGBM treated with apatinib and TMZ. We enrolled 22 rGBMs treated with apatinib in combination with TMZ and collected their tissue samples for RNA transcriptome analysis by the Nanostring nCounter platform. The response group had 40 differentially expressed genes compared to the non-response group, with significantly up-regulated expression of genes related to endothelial cells and apoptosis. Enrichment analysis revealed that signaling pathways related to cell proliferation were down-regulated in the response group. In terms of prognosis, there were 16 differential expressed genes in the long-survival benefit group compared with the short-survival benefit group, and four tumor progression-associated genes were also down-regulated in response group expression. Hypoxia related-genes was significantly up-regulated in the long survival benefit group. Enrichment analysis showed that genes related to cell proliferation were also down-regulated in the long-survival benefit group, while the expression of signaling pathway genes related to cell activation, and immune response was significantly up-regulated. Our study suggests that the combination of apatinib and TMZ may potentially provide clinical benefits in treating rGBM by modulating genes associated with cell proliferation, promoting apoptosis, regulating hypoxia, and enhancing immune response within the tumor microenvironment.