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Bioinformatics and survival analysis of glia maturation factor-γ in pan-cancers
Aihua Lan1, Chunxia Ren2, Xiaoling Wang2
1Central Laboratory, the Fifth People's Hospital of Shanghai, Fudan University, Shanghai, 200240, China.
Background:
Glia maturation factor-γ (GMFG) is reported to inhibit the actin nucleation through binding to the actin-related protein-2/3 complex (Arp2/3). Considering the main function of GMFG in actin remodeling, which is vital for immune response, angiogenesis, cell division and motility, GMFG is supposed to have important roles in tumor development, while up to now, only two studies described the role of GMFG in cancers. By investigating the clinical values of GMFG using The Cancer Genome Atlas (TCGA) data and the functional mechanisms of GMFG through analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments, this study was aimed to better understand the impact of GMFG in pan-cancers and to draw more attentions for the future research of GMFG.
Methods:
RNA-seq and clinical data of cancer patients were collected from TCGA and analyzed by the Kaplan-Meier methods. GO and KEGG analyses were conducted using the online tools from the Database for Annotation, Visualization and Integrated Discovery (DAVID).
Results:
Compared to the corresponding normal samples, GMFG was significantly upregulated in glioblastoma (GBM), kidney clear cell carcinoma (KIRC), lower grade glioma (LGG), acute myeloid leukemia (LAML), and pancreatic cancer (PAAD), testicular cancer (TGCT), but was downregulated in kidney chromophobe (KICH), lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) (P < 0.05 for all). High expression of GMFG predicted worse OS in GBM (HR = 1.5, P = 0.017), LGG (HR = 2.2, P < 0.001), LUSC (HR = 1.4, P = 0.022) and ocular melanomas (UVM) (HR = 7, P < 0.001), as well as worse DFS in LGG (HR = 1.8, P < 0.001) and prostate cancer (PRAD) (HR = 1.9, P = 0.004). In contrast, high expression of GMFG was associated with better OS in skin cutaneous melanoma (SKCM) (HR = 0.59, P < 0.001) and thymoma (THYM) (HR = 0.098, P = 0.031), as well as better DFS in bile duct cancer (CHOL) (HR = 0.2, P = 0.003). GMFG was mainly involved in the immune response, protein binding and cytokine-cytokine receptor interaction pathways, and was positively associated with multiple immunomodulators in most cancers.
Conclusion:
Our study preliminarily identified that GMFG may cause different survivals for different cancers through modulating tumor progression, immune response status and tissue-specific tumor microenvironment (TME).
Insights
Glia maturation factor-gamma (GMFG) expression impacts cancer survival differently across various cancer types. This study investigates GMFG
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Glia maturation factor-gamma (GMFG) influences actin remodeling, crucial for cellular processes like immune response and motility.
- Limited research exists on GMFG's role in cancer development, despite its potential involvement.
- This study aims to elucidate GMFG's impact on pan-cancer progression.
Purpose of the Study:
- To investigate the clinical significance of GMFG expression in various cancers using TCGA data.
- To explore the functional mechanisms underlying GMFG's role in cancer through pathway enrichment analyses.
- To provide a comprehensive understanding of GMFG's pan-cancer impact and guide future research.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) database for RNA-seq and clinical data analysis.
- Employed Kaplan-Meier methods to assess survival outcomes based on GMFG expression.
- Conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses using DAVID tools.
Main Results:
- GMFG expression varied significantly across cancer types, being upregulated in some (e.g., GBM, KIRC, PAAD) and downregulated in others (e.g., KICH, LUAD, LUSC).
- High GMFG expression correlated with worse overall survival (OS) and disease-free survival (DFS) in several cancers (e.g., GBM, LGG, LUSC, PRAD).
- Conversely, high GMFG expression was associated with better OS in SKCM and THYM, and better DFS in CHOL, and was linked to immune response pathways and immunomodulators.
Conclusions:
- GMFG exhibits differential effects on patient survival across various cancer types.
- GMFG influences cancer progression, immune response, and the tumor microenvironment.
- Further research into GMFG's multifaceted roles in oncology is warranted.
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