PDF(Pubmed)
Abstract：
UNASSIGNED: Pancreatic adenocarcinoma (PAAD) is a formidable challenge in oncology research, with a complex pathogenesis that requires to be explored. Major Vault Protein (MVP) is the principal structural component of the vault complex, and its expression level is remarkably upregulated in various cancers. Extensive investigations have been conducted to explore the role of MVP in specific cancer contexts, yet the potential molecular mechanisms and biological functions of MVP in PAAD still remain considerably elusive. This study aims to explore the role of MVP as a novel immune-related biomarker in the pathogenesis and clinical treatment of PAAD.
UNASSIGNED: Gene expression data and clinical information were collected from TCGA, GTEx and GEO databases. Survival, prognostic and functional enrichment analysis were employed with R software. Immunological correlation analysis was performed using TIMER2.0, TIDE scores, TISIDB and TISCH. Epigenetic analysis was implemented by MethSurv, CPTAC, UALCAN, and cBioPortal. Drug analysis was conducted using Enrichr and CellMiner. Moreover, cellular experiments, like RNA interference, qRT-PCR, Western blot, cell cycle analysis, cell apoptosis analysis, colony formation assay, transwell assay, and wound healing assay, were performed for verifying the functional properties of MVP in the PAAD progression.
UNASSIGNED: We demonstrated an abnormally upregulated expression of MVP in PAAD tissues, which notably correlated with an adverse prognosis in PAAD patients. Functional analysis suggested the conceivable involvement of MVP in immune modulation, and immunotherapy. Additionally, we identified genetic alterations, reduced promoter methylation, and heightened phosphorylation in MVP. We also clarified Suloctidil and Tetradioxin as the most notable potential drugs targeting MVP in PAAD. Moreover, our experimental observations consistently highlighted the significant impact of MVP deficiency on impeding PAAD cell proliferation, inhibiting cell migration, and accelerating cell apoptosis. Interestingly, a potential link between MVP and ERK or AKT pathways was displayed, which opens new avenues for further exploration of the molecular mechanisms of MVP-targeted therapies in PAAD.
UNASSIGNED: This study systematically describes MVP as an immune-related biomarker with remarkable potential for predicting the prognosis, tumor progression and immunotherapeutic efficacy in PAAD.
UNASSIGNED: Gene expression data and clinical information were collected from TCGA, GTEx and GEO databases. Survival, prognostic and functional enrichment analysis were employed with R software. Immunological correlation analysis was performed using TIMER2.0, TIDE scores, TISIDB and TISCH. Epigenetic analysis was implemented by MethSurv, CPTAC, UALCAN, and cBioPortal. Drug analysis was conducted using Enrichr and CellMiner. Moreover, cellular experiments, like RNA interference, qRT-PCR, Western blot, cell cycle analysis, cell apoptosis analysis, colony formation assay, transwell assay, and wound healing assay, were performed for verifying the functional properties of MVP in the PAAD progression.
UNASSIGNED: We demonstrated an abnormally upregulated expression of MVP in PAAD tissues, which notably correlated with an adverse prognosis in PAAD patients. Functional analysis suggested the conceivable involvement of MVP in immune modulation, and immunotherapy. Additionally, we identified genetic alterations, reduced promoter methylation, and heightened phosphorylation in MVP. We also clarified Suloctidil and Tetradioxin as the most notable potential drugs targeting MVP in PAAD. Moreover, our experimental observations consistently highlighted the significant impact of MVP deficiency on impeding PAAD cell proliferation, inhibiting cell migration, and accelerating cell apoptosis. Interestingly, a potential link between MVP and ERK or AKT pathways was displayed, which opens new avenues for further exploration of the molecular mechanisms of MVP-targeted therapies in PAAD.
UNASSIGNED: This study systematically describes MVP as an immune-related biomarker with remarkable potential for predicting the prognosis, tumor progression and immunotherapeutic efficacy in PAAD.
摘要：
■胰腺腺癌（PAAD）是肿瘤学研究中的一个巨大挑战，具有复杂的发病机制，需要探索。主要库蛋白(MVP)是库复合体的主要结构成分,其表达水平在各种癌症中显著上调。已经进行了广泛的研究，以探索MVP在特定癌症环境中的作用。然而，MVP在PAAD中的潜在分子机制和生物学功能仍然相当难以捉摸。本研究旨在探讨MVP作为一种新型免疫相关生物标志物在PAAD发病机制及临床治疗中的作用。
■从TCGA收集基因表达数据和临床信息，GTEx和GEO数据库。生存,用R软件进行预后和功能富集分析。使用TIMER2.0，TIDE评分，TISIB和TISCH。表观遗传分析由MethSurv实施，CPTAC,UALCAN,和cBioPortal。使用Enrichr和CellMiner进行药物分析。此外，细胞实验,比如RNA干扰，qRT-PCR,蛋白质印迹,细胞周期分析,细胞凋亡分析，集落形成试验,transwell分析，和伤口愈合试验，进行验证MVP在PAAD进展中的功能特性。
■我们证明了PAAD组织中MVP的异常上调表达，这与PAAD患者的不良预后显着相关。功能分析表明MVP可能参与免疫调节，和免疫疗法。此外,我们发现了基因改变，降低启动子甲基化，MVP的磷酸化增强。我们还澄清了Suloctidil和Tetradioxin是PAAD中最著名的靶向MVP的潜在药物。此外，我们的实验观察一致强调了MVP缺乏对阻碍PAAD细胞增殖的显著影响，抑制细胞迁移，加速细胞凋亡。有趣的是,显示了MVP和ERK或AKT通路之间的潜在联系，这为进一步探索PAAD中MVP靶向治疗的分子机制开辟了新的途径。
■这项研究系统地描述了MVP作为一种免疫相关的生物标志物，具有预测预后的巨大潜力，PAAD的肿瘤进展和免疫治疗疗效。
■从TCGA收集基因表达数据和临床信息，GTEx和GEO数据库。生存,用R软件进行预后和功能富集分析。使用TIMER2.0，TIDE评分，TISIB和TISCH。表观遗传分析由MethSurv实施，CPTAC,UALCAN,和cBioPortal。使用Enrichr和CellMiner进行药物分析。此外，细胞实验,比如RNA干扰，qRT-PCR,蛋白质印迹,细胞周期分析,细胞凋亡分析，集落形成试验,transwell分析，和伤口愈合试验，进行验证MVP在PAAD进展中的功能特性。
■我们证明了PAAD组织中MVP的异常上调表达，这与PAAD患者的不良预后显着相关。功能分析表明MVP可能参与免疫调节，和免疫疗法。此外,我们发现了基因改变，降低启动子甲基化，MVP的磷酸化增强。我们还澄清了Suloctidil和Tetradioxin是PAAD中最著名的靶向MVP的潜在药物。此外，我们的实验观察一致强调了MVP缺乏对阻碍PAAD细胞增殖的显著影响，抑制细胞迁移，加速细胞凋亡。有趣的是,显示了MVP和ERK或AKT通路之间的潜在联系，这为进一步探索PAAD中MVP靶向治疗的分子机制开辟了新的途径。
■这项研究系统地描述了MVP作为一种免疫相关的生物标志物，具有预测预后的巨大潜力，PAAD的肿瘤进展和免疫治疗疗效。
