Scouting for common genes in the heterogenous hypoxic tumor microenvironment and their validation in glioblastoma

Investigating the therapeutic and prognostic potential of genes in the heterogeneous hypoxic niche of glioblastoma. We have analyzed RNA expression of U87MG cells cultured in hypoxia compared to normoxia. Common differentially expressed genes (DEGs) from GSE45301 and GSE18494 and their functional enrichment was performed using MetaScape and PANTHER. Hub genes and their ontology were identified using MCode cytoHubba and ClueGO and validated with GlioVis, Oncomine, HPA and PrognoScan. Using the GEO2R analysis of GSE45301 and GSE18494 datasets, we have found a total of 246 common DEGs (180 upregulated and 66 downregulated) and identified 2 significant modules involved in ribosome biogenesis and TNF signaling. Meta-analysis of key genes of each module in cytoHubba identified 17 hub genes (ATF3, BYSL, DUSP1, EGFR, JUN, ETS1, LYAR, NIP7, NOLC1, NOP2, NOP56, PNO1, RRS1, TNFAIP3, TNFRSF1B, UTP15, VEGFA). Of the 17 hub genes, ATF3, BYSL, EGFR, JUN, NIP7, NOLC1, PNO1, RRS1, TNFAIP3 and VEGFA were identified as hypoxia signatures associated with poor prognosis in Glioma. Ribosome biogenesis emerged as a vital contender of possible therapeutic potential with BYSL, NIP7, NOLC1, PNO1 and RRS1 showing prognostic value.

The online version contains supplementary material available at 10.1007/s13205-021-02987-2.