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Comparative Analysis of the GNAI Family Genes in Glioblastoma through Transcriptomics and Single-Cell Technologies
Ahmad Raza1, Meng-Chi Yen2,3, Gangga Anuraga4
1Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.
Abstract:
Glioblastoma multiforme (GBM) is one of the most aggressive cancers with a low overall survival rate. The treatment of GBM is challenging due to the presence of the blood-brain barrier (BBB), which hinders drug delivery. Invasive procedures alone are not effective at completely removing such tumors. Hence, identifying the crucial pathways and biomarkers for the treatment of GBM is of prime importance. We conducted this study to identify the pathways associated with GBM. We used The Cancer Genome Atlas (TCGA) GBM genomic dataset to identify differentially expressed genes (DEGs). We investigated the prognostic values of the guanine nucleotide-binding protein G(i) alpha subunit (GNAI) family of genes in GBM using a Chinese Glioma Genome Atlas (CGGA) dataset. Within this dataset, we observed the association in the tumor microenvironment between the gene expression of GNAI subunit 3 (GNAI3) and a poor prognosis. MetaCore and gene ontology (GO) analyses were conducted to explore the role of GNAI3 in co-expressed genes and associated signaling pathways using a transcript analysis. Notable pathways included "Cytoskeleton remodeling regulation of actin cytoskeleton organization by the kinase effectors of Rho GTPases" and "Immune response B cell antigen receptor (BCR) pathway". A single-cell analysis was used to assess GNAI3 expression in GBM. The results demonstrated that GNAI family genes, specifically GNAI3, were significantly associated with carcinogenesis and malignancy in GBM patients. Our findings suggest that the GNAI3 gene holds potential as a prognostic biomarker for GBM.
Insights
Glioblastoma multiforme (GBM) is a challenging cancer. Researchers found the GNAI3 gene is linked to poor prognosis, suggesting it could be a new biomarker for GBM treatment.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Glioblastoma multiforme (GBM) is a highly aggressive brain cancer with poor patient survival rates.
- Current GBM treatments face challenges due to the blood-brain barrier (BBB) and incomplete tumor removal via surgery.
- Identifying novel therapeutic targets and prognostic biomarkers is crucial for improving GBM patient outcomes.
Purpose of the Study:
- To identify key molecular pathways and potential biomarkers associated with Glioblastoma Multiforme (GBM).
- To investigate the prognostic significance of the guanine nucleotide-binding protein G(i) alpha subunit (GNAI) gene family in GBM.
- To explore the role of GNAI3 in GBM pathogenesis and its potential as a prognostic biomarker.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) GBM dataset to identify differentially expressed genes (DEGs).
- Analyzed the Chinese Glioma Genome Atlas (CGGA) dataset to assess the prognostic value of GNAI family genes, focusing on GNAI3.
- Employed MetaCore, gene ontology (GO) analysis, and single-cell analysis to investigate GNAI3's role in co-expressed genes and signaling pathways.
Main Results:
- The study identified a significant association between GNAI3 gene expression and poor prognosis in GBM patients within the tumor microenvironment.
- Pathway analysis revealed GNAI3's involvement in crucial cellular processes, including cytoskeleton remodeling and immune response pathways (e.g., B cell receptor pathway).
- GNAI family genes, particularly GNAI3, were found to be significantly correlated with the carcinogenesis and malignancy of GBM.
Conclusions:
- The GNAI gene family, especially GNAI3, plays a significant role in the development and progression of Glioblastoma Multiforme.
- GNAI3 demonstrates potential as a valuable prognostic biomarker for GBM patients.
- Targeting GNAI3 pathways may offer new therapeutic strategies for managing GBM.
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