Dynamine 3作为胰腺癌诊断和预后的生物标志物:对早期发现和靶向治疗的意义。

IF 2 4区 医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Biomarkers Pub Date : 2025-03-01 Epub Date: 2025-02-04 DOI:10.1080/1354750X.2025.2458104
Fatih Yay, Hasan Çağrı Yıldırım, Fatih Kuş, Şuayib Yalçın
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引用次数: 0

摘要

背景:动力蛋白被定义为一组具有GTPase活性的分子,在内吞囊泡和高尔基体的形成中起作用。其中,DNM3因其抑瘤作用在肿瘤学领域得到认可。基于此,本研究旨在利用生物信息学数据库探讨DNM3基因对胰腺癌患者的影响。材料与方法:采用the gene expression Omnibus (GEO)上的TCGA TARGET GTEx研究,对UCSC Xena、GSE196009、GSE211398、GSE151580数据集进行差异基因表达分析;利用GEPIA2分析不同阶段的基因表达变化;根据临床和病理特征分析基因表达变化,采用UALCAN法;总生存期(OS)分析采用Kaplan-Meier绘图仪;基因改变分析使用cbiopportal;免疫细胞浸润分析采用肿瘤免疫估计资源(Tumor immune Estimation Resource, TIMER)和TIMER2.0;蛋白相互作用和基因富集分析采用STRING;富集分析使用enrichment;基因集相关富集分析采用Gscore对GSE15471进行分析;DNM3基因在胰腺癌细胞系中的重要性采用DepMap;mirna的检测采用miRDB;采用ENCORI进行基因-miRNA相关性及miRNA预后分析。结果:在胰腺腺癌(PAAD)队列中,DNM3基因在肿瘤样本中的表达较高,不同肿瘤分期间表达差异无统计学意义。高水平的DNM3基因表达与PAAD患者较长的OS相关。DNM3基因表达与b细胞、CD + T细胞浸润呈弱正相关,与CD8+ T细胞、巨噬细胞、中性粒细胞、树突状细胞浸润呈中度正相关。QUANTISEQ浸润NK细胞、TIMER浸润cd4 + T细胞、CIBERSORT-ABS浸润T细胞调节细胞(Tregs)与DNM3基因表达呈正相关,降低预后风险。XCELL浸润的普通淋巴样祖细胞和TIDE浸润的MDSC与DNM3基因表达和预后风险增加呈负相关。通过QUANTISEQ检测巨噬细胞M1与DNM3基因表达呈正相关,并增加预后风险。DNM3基因似乎与炎症和免疫系统相关的各种途径有关。175例患者中有5例检测到DNM3基因扩增。在细菌侵袭上皮细胞、内吞作用、内分泌等因子调节的钙重吸收、突触囊泡循环、磷脂酶D信号通路等途径中均观察到富集。根据Gscore, DNM3基因与Fc epsilon RI信号通路、HALLMARK MTORC1信号通路、HALLMARK上皮间充质转化基因组相关。ENCORI结果显示,DNM3基因与hsa-miR-203a-3p呈负相关,且该miRNA表达升高与PAAD患者预后不良相关。结论:DNM3基因可能在胰腺癌中发挥抑瘤作用,其作用类似于其他恶性肿瘤。免疫细胞的作用在这种效应中可能也很重要。然而,需要体外研究来阐明胰腺癌触发的机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Dynamine 3 as a diagnostic and prognostic biomarker in pancreatic cancer: Implications for early detection and targeted therapy.

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.

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来源期刊
Biomarkers
Biomarkers 医学-毒理学
CiteScore
5.00
自引率
3.80%
发文量
140
审稿时长
3 months
期刊介绍: The journal Biomarkers brings together all aspects of the rapidly growing field of biomarker research, encompassing their various uses and applications in one essential source. Biomarkers provides a vital forum for the exchange of ideas and concepts in all areas of biomarker research. High quality papers in four main areas are accepted and manuscripts describing novel biomarkers and their subsequent validation are especially encouraged: • Biomarkers of disease • Biomarkers of exposure • Biomarkers of response • Biomarkers of susceptibility Manuscripts can describe biomarkers measured in humans or other animals in vivo or in vitro. Biomarkers will consider publishing negative data from studies of biomarkers of susceptibility in human populations.
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