Identification of Key Candidate Proteins and Pathways Associated with Temozolomide Resistance in Glioblastoma Based
Guo-Zhong Yi1,2, Wei Xiang3, Wen-Yan Feng4
1Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
Abstract:
TMZ resistance remains one of the main reasons why treatment of glioblastoma (GBM) fails. In order to investigate the underlying proteins and pathways associated with TMZ resistance, we conducted a cytoplasmic proteome research of U87 cells treated with TMZ for 1 week, followed by differentially expressed proteins (DEPs) screening, KEGG pathway analysis, protein-protein interaction (PPI) network construction, and validation of key candidate proteins in TCGA dataset. A total of 161 DEPs including 65 upregulated proteins and 96 downregulated proteins were identified. Upregulated DEPs were mainly related to regulation in actin cytoskeleton, focal adhesion, and phagosome and PI3K-AKT signaling pathways which were consistent with our previous studies. Further, the most significant module consisted of 28 downregulated proteins that were filtered from the PPI network, and 9 proteins (DHX9, HNRNPR, RPL3, HNRNPA3, SF1, DDX5, EIF5B, BTF3, and RPL8) among them were identified as the key candidate proteins, which were significantly associated with prognosis of GBM patients and mainly involved in ribosome and spliceosome pathway. Taking the above into consideration, we firstly identified candidate proteins and pathways associated with TMZ resistance in GBM using proteomics and bioinformatic analysis, and these proteins could be potential biomarkers for prevention or prediction of TMZ resistance in the future.
Insights
This study identified key proteins and pathways linked to glioblastoma (GBM) resistance to temozolomide (TMZ). These findings may lead to new biomarkers for predicting or preventing TMZ resistance in GBM patients.
Area of Science:
- Oncology
- Proteomics
- Bioinformatics
Background:
- Temozolomide (TMZ) resistance is a major challenge in glioblastoma (GBM) treatment.
- Identifying molecular mechanisms of resistance is crucial for improving patient outcomes.
Purpose of the Study:
- To investigate proteins and pathways associated with TMZ resistance in GBM.
- To identify potential biomarkers for predicting or preventing TMZ resistance.
Main Methods:
- Proteomic analysis of U87 cells treated with TMZ.
- Bioinformatic analyses including KEGG pathway and protein-protein interaction (PPI) network construction.
- Validation of candidate proteins using The Cancer Genome Atlas (TCGA) dataset.
Main Results:
- Identified 161 differentially expressed proteins (DEPs) in TMZ-treated U87 cells.
- Upregulated DEPs were associated with actin cytoskeleton, focal adhesion, phagosome, and PI3K-AKT signaling pathways.
- Nine key candidate proteins (DHX9, HNRNPR, RPL3, HNRNPA3, SF1, DDX5, EIF5B, BTF3, RPL8) involved in ribosome and spliceosome pathways were identified and associated with GBM patient prognosis.
Conclusions:
- This study provides novel insights into the molecular underpinnings of TMZ resistance in GBM.
- The identified proteins represent potential biomarkers for predicting or preventing TMZ resistance in glioblastoma.
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