Tumor Microenvironment and Genes Affecting the Prognosis of Temozolomide-Treated Glioblastoma

Abstract

Glioblastoma (GBM) is the most frequent primary brain tumor in adults and has a poor prognosis due to its resistance to Temozolomide (TMZ). However, there is limited research regarding the tumor microenvironment and genes related to the prognosis of TMZ-treated GBM patients. This study aimed to identify putative transcriptomic biomarkers with predictive value in patients with GBM who were treated with TMZ. Publicly available datasets from The Cancer Genome Atlas and Gene Expression Omnibus were analyzed using CIBERSORTx and Weighted Gene Co-expression Network Analysis (WGCNA) to obtain types of highly expressed cell types and gene clusters. Differentially Expressed Genes analysis was performed and was intersected with the WGCNA results to obtain a candidate gene list. Cox proportional-hazard survival analysis was performed to acquire genes related to the prognosis of TMZ-treated GBM patients. Inflammatory microglial cells, dendritic cells, myeloid cells, and glioma stem cells were highly expressed in GBM tissue, and ACP7, EPPK1, PCDHA8, RHOD, DRC1, ZIC3, and PRLR were significantly associated with survival. While the listed genes have been previously reported to be related to glioblastoma or other types of cancer, ACP7 was identified as a novel gene related to the prognosis of GBM. These findings may have potential implications for developing a diagnostic tool to predict GBM resistance and optimize treatment decisions.

Integrated analysis of single‐cell sequencing and weighted co‐expression network identifies a novel signature based on cellular senescence‐related genes to predict prognosis in glioblastoma

“…DRC1 is a crucial gene that is regulated during the cell cycle and is vital in DNA replication 43 . In addition, DRC1 could affect survival in GBM, which is consistent with our results 44 . CCDC13, a newly identified centriolar satellite protein in humans, is crucial in promoting ciliogenesis and maintaining the stability of genome 45 .…”

“…43 In addition, DRC1 could affect survival in GBM, which is consistent with our results. 44 CCDC13, a newly identified centriolar satellite protein in humans, is crucial in promoting ciliogenesis and maintaining the stability of genome. 45 WDR63 acts as a suppressor of cell migration, invasion, and metastasis by inhibiting Arp2/3-mediated actin polymerization, 46 which holds significance in the progression of lung cancer.…”

The Influence of Race/Ethnicity on the Transcriptomic Landscape of Uterine Fibroids

“…Here, we report greater differential expression of EZH2 in tumors from Black patients than in those from White patients, indicating greater epigenetic gene modification in this group. ACP7 is an acid phosphatase with marked relative expression in fibroids in all groups but more so in Blacks; the physiologic function of this gene is unexplored, except in one study showing an association with glioblastoma survival [36].…”