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Published on: April 18, 2015
Dynamine 3 as a diagnostic and prognostic biomarker in pancreatic cancer: Implications for early detection and
Fatih Yay1, Hasan Çağrı Yıldırım2, Fatih Kuş3
1Clinical Biochemistry Laboratory, Nigde Omer Halisdemir University Training and Research Hospital, Nigde, Turkey.
Background:
Dynamins are defined as a group of molecules with GTPase activity. Among them, DNM3 has gained recognition in oncology for its tumor suppressor role. Based on this, the aim of this study is to investigate the effects of the DNM3 gene in patients diagnosed with pancreatic cancer using bioinformatics databases.
Materials And Methods:
For differential gene expression analysis, TCGA TARGET GTEx study on the UCSC Xena and GEO datasets were utilized; for the analysis of changes in gene expression according to clinical and pathological characteristics, UALCAN was employed; for Overall Survival (OS) analysis, Kaplan-Meier Plotter was used; for gene alteration analysis, cBioPortal was utilized; for immune cell infiltration analysis, Tumor Immune Estimation Resource (TIMER) and TIMER2.0 were employed; for enrichment analyses Enrichr was used; for Gene Set Correlation Enrichment Analysis Gscore was used on GSE15471; for essentiality of DNM3 gene in pancratic cancer cell lines DepMap was used; and for the detection of miRNAs, miRDB was utilized; ENCORI was used for gene-miRNA correlation and miRNA prognosis analyses.
Results:
In the pancreatic adenocarcinoma (PAAD) cohort, DNM3 gene expression was higher in tumor samples, and there was no significant difference in expression among cancer stages. High levels of DNM3 gene expression were associated with longer OS in PAAD. A weak positive correlation was observed between DNM3 gene expression and B-Cell and CD4+ T Cell infiltrations, while a moderate positive correlation was found with CD8+ T Cell, Macrophage, Neutrophil, and Dendritic Cell infiltrations in TIMER. NK cell by QUANTISEQ, CD 4+ T Cell by TIMER, T cell regulatory (Tregs) by CIBERSORT-ABS infiltrations were positively associated with DNM3 gene expression and decreased risk in prognosis. Common lymphoid progenitor by XCELL and MDSC by TIDE infiltrations were negatively associated with DNM3 gene expression and increased risk of prognosis. Macrophage M1 by QUANTISEQ was positively associated with DNM3 gene expression and increased risk in prognosis. DNM3 gene appears to be associated with various pathways related to inflammation and the immune system. Amplification of the DNM3 gene was detected in 5 out of 175 patients. Enrichment was observed in pathways such as bacterial invasion of epithelial cells, endocytosis, endocrine and other factor-regulated calcium reabsorption, synaptic vesicle cycle, and phospholipase D signaling pathway. According to Gscore, DNM3 gene was associated with Fc epsilon RI signaling pathway, HALLMARK MTORC1 SIGNALING, HALLMARK EPITHELIAL MESENCHYMAL TRANSITION gene sets. According to ENCORI, DNM3 gene was negatively correlated with hsa-miR-203a-3p and increased expression of this miRNA was associated with adverse prognosis in PAAD.
Conclusions:
The DNM3 gene may play a tumor suppressor role in pancreatic cancer, similar to its role in other malignancies. The contribution of immune cells may also be significant in this effect. However, in vitro studies are needed to elucidate the mechanisms triggered in pancreatic cancer.
Insights
The DNM3 gene shows potential as a tumor suppressor in pancreatic cancer, correlating with improved survival and immune cell infiltration. Further in vitro studies are needed to confirm its mechanisms.
Area of Science:
- Oncology
- Genetics
- Bioinformatics
- Immunology
Background:
- Dynamins are GTPase proteins, with DNM3 recognized for its tumor suppressor functions in cancer.
- Pancreatic cancer is a significant health concern, necessitating research into novel therapeutic targets and biomarkers.
- Understanding the role of DNM3 in pancreatic cancer could offer new insights into disease mechanisms and treatment strategies.
Purpose of the Study:
- To investigate the role and impact of the DNM3 gene in pancreatic cancer patients.
- To analyze DNM3 gene expression, its correlation with clinical/pathological features, and its prognostic significance.
- To explore the association of DNM3 with immune cell infiltration and relevant biological pathways in pancreatic cancer.
Main Methods:
- Utilized TCGA TARGET GTEx, UCSC Xena, GEO, UALCAN, and Kaplan-Meier Plotter for gene expression and survival analyses.
- Employed cBioPortal for gene alteration analysis and TIMER/TIMER2.0 for immune cell infiltration assessment.
- Conducted enrichment analyses using Enrichr, Gscore, DepMap, miRDB, and ENCORI for pathway, miRNA, and correlation studies.
Main Results:
- DNM3 expression was elevated in pancreatic adenocarcinoma (PAAD) tumors and associated with longer Overall Survival (OS).
- DNM3 showed correlations with various immune cell infiltrations, including CD8+ T cells, macrophages, and neutrophils.
- Gene enrichment analysis revealed associations with pathways like bacterial invasion, endocytosis, and immune signaling; DNM3 negatively correlated with hsa-miR-203a-3p.
Conclusions:
- DNM3 may function as a tumor suppressor in pancreatic cancer, potentially mediated by immune cell interactions.
- The findings suggest DNM3's involvement in immune and inflammatory pathways within the pancreatic tumor microenvironment.
- Further in vitro investigations are required to elucidate the precise molecular mechanisms of DNM3 in pancreatic cancer.
