Integrated analysis identified core signal pathways and hypoxic characteristics of human glioblastoma

Abstract

As a hallmark for glioblastoma (GBM), high heterogeneity causes a variety of phenotypes and therapeutic responses among GBM patients, and it contributes to treatment failure. Moreover, hypoxia is a predominant feature of GBM and contributes greatly to its phenotype. To analyse the landscape of gene expression and hypoxic characteristics of GBM cells and their clinical significance in GBM patients, we performed transcriptome analysis of the GBM cell line U87‐MG and the normal glial cell line HEB under normoxia and hypoxia conditions, with the results of which were analysed using established gene ontology databases as well as The Cancer Genome Atlas and the Cancer Cell Line Encyclopedia. We revealed core signal pathways, including inflammation, angiogenesis and migration, and for the first time mapped the components of the toll‐like receptor 6 pathway in GBM cells. Moreover, by investigating the signal pathways involved in homoeostasis, proliferation and adenosine triphosphate metabolism, the critical response of GBM to hypoxia was clarified. Experiments with cell lines, patient serum and tissue identified IL1B, CSF3 and TIMP1 as potential plasma markers and VIM, STC1, TGFB1 and HMOX1 as potential biopsy markers for GBM. In conclusion, our study provided a comprehensive understanding for signal pathways and hypoxic characteristics of GBM and identified new biomarkers for GBM patients.

miR-6745-TIMP1 axis inhibits cell growth and metastasis in gastric cancer

“…TIMP-1 has both MMPs-dependent anti-proteolytic activity and MMP-independent cell growth activity [ 23 ]. Our results show that TIMP1 promotes the occurrence and development of GC, which is consistent with previous reports about TIMP1 as an oncogene in other cancers, including breast cancer [ 24 ], colon cancer [ 10 ], glioblastoma [ 25 ], and non-small cell lung cancer [ 26 ].…”

Bulk and Single-Cell Transcriptome Analyses Revealed That the Pyroptosis of Glioma-Associated Macrophages Participates in Tumor Progression and Immunosuppression

“…For example, in pancreatic ductal adenocarcinoma (PDA) and head and neck squamous cell carcinoma (HNSCC), inflammasomes of tumor-associated macrophages activate caspase-1 and mediate the cleavage of GSDMD and the release of mature IL1 β , resulting in the suppression of CD8+ T cells [ 13 , 14 ]. Although inflammasome-mediated pyroptosis in glioma has not been reported, IL1 β has been shown to be a serum marker in glioblastoma [ 16 , 17 ], which prompted us to explore potential pyroptosis pathways in glioma.…”

“…As an important molecular marker of pyroptosis [9], IL1β is generally released from the pore formed by oligomerized GSDMD [12] and has been shown to be closely associated with the formation of an immunosuppressive microenvironment in several tumor types [13][14][15]. Notably, several studies have shown that the proinflammatory cytokine IL1β is significantly elevated in the serum of glioblastoma (GBM) patients and serves as a potential serum marker for this type of disease [16,17]. In addition, a very recent study showed that monocyte-derived macrophages in gliomas secrete IL1β in response to tumor cell induction, while Il1b knockdown significantly prolonged the survival time of primary glioma mice [18].…”

A novel necroptosis-related gene signature for predict prognosis of glioma based on single-cell and bulk RNA sequencing

“…Thioredoxin-interacting protein ( TXNIP ) was reported as a tumor-suppressor gene in glioma ( Zhang et al, 2017 ). VIM had been identified as a potential biopsy marker for glioma in several bioinformatics analyses ( Gao et al, 2019 ; Wang J. J. et al, 2021 ; Herrera-Oropeza et al, 2021 ). Also, our results corroborated these analyses.…”