关键词: SLC31A1 biomarker bladder cancer diagnostic prognostic

Mesh : Aged Female Humans Male Middle Aged Biomarkers, Tumor / genetics metabolism Copper Transporter 1 / genetics metabolism Disease Progression DNA Methylation Gene Expression Regulation, Neoplastic Mutation Prognosis Promoter Regions, Genetic Up-Regulation Urinary Bladder Neoplasms / drug therapy genetics pathology

来  源:   DOI:10.1177/03946320241240706   PDF(Pubmed)

Abstract:
Introduction: Bladder cancer represents a significant public health concern with diverse genetic alterations influencing disease onset, progression, and therapy response. In this study, we explore the multifaceted role of Solute Carrier Family 31 Member 1 (SLC31A1) in bladder cancer, a pivotal gene involved in copper homeostasis. Methods: Our research involved analyzing the SLC31A1 gene expression via RT-qPCR, promoter methylation via targeted bisulfite sequencing, and mutational status via Next Generation Sequencing (NGS) using the clinical samples sourced by the local bladder cancer patients. Later on, The Cancer Genome Atlas (TCGA) datasets were utilized for validation purposes. Moreover, prognostic significance, gene enrichment terms, and therapeutic drugs of SLC31A1 were also explored using KM Plotter, DAVID, and DrugBank databases. Results: We observed that SLC31A1 was significantly up-regulated at both the mRNA and protein levels in bladder cancer tissue samples, suggesting its potential involvement in bladder cancer development and progression. Furthermore, our investigation into the methylation status revealed that SLC31A1 was significantly hypomethylated in bladder cancer tissues, which may contribute to its overexpression. The ROC analysis of the SLC31A1 gene indicated promising diagnostic potential, emphasizing its relevance in distinguishing bladder cancer patients from normal individuals. However, it is crucial to consider other factors such as cancer stage, metastasis, and recurrence for a more accurate evaluation in the clinical context. Interestingly, mutational analysis of SLC31A1 demonstrated only benign mutations, indicating their unknown role in the SLC31A1 disruption. In addition to its diagnostic value, high SLC31A1 expression was associated with poorer overall survival (OS) in bladder cancer patients, shedding light on its prognostic relevance. Gene enrichment analysis indicated that SLC31A1 could influence metabolic and copper-related processes, further underscoring its role in bladder cancer. Lastly, we explored the DrugBank database to identify potential therapeutic agents capable of reducing SLC31A1 expression. Our findings unveiled six important drugs with the potential to target SLC31A1 as a treatment strategy. Conclusion: Our comprehensive investigation highlights SLC31A1 as a promising biomarker for bladder cancer development, progression, and therapy.
摘要:
简介:膀胱癌是一个重要的公共卫生问题,具有影响疾病发作的多种遗传改变,programming,和治疗反应。在这项研究中,我们探讨了溶质载体家族31成员1(SLC31A1)在膀胱癌中的多方面作用,参与铜稳态的关键基因。方法:我们的研究涉及通过RT-qPCR分析SLC31A1基因的表达,通过靶向亚硫酸氢盐测序启动子甲基化,使用来自局部膀胱癌患者的临床样品,通过下一代测序(NGS)进行突变状态。稍后,癌症基因组图谱(TCGA)数据集用于验证目的。此外,预后意义,基因富集术语,还使用KM绘图仪探索了SLC31A1的治疗药物,大卫,和DrugBank数据库。结果:我们观察到SLC31A1在膀胱癌组织样本的mRNA和蛋白水平均显著上调,提示其可能参与膀胱癌的发展和进展。此外,我们对甲基化状态的调查显示,SLC31A1在膀胱癌组织中显著低甲基化,这可能有助于其过度表达。SLC31A1基因的ROC分析显示有希望的诊断潜力,强调其在区分膀胱癌患者与正常人中的相关性。然而,考虑其他因素,如癌症分期,转移,和复发,以便在临床上进行更准确的评估。有趣的是,SLC31A1的突变分析表明只有良性突变,表明它们在SLC31A1破坏中的未知作用。除了它的诊断价值,SLC31A1高表达与膀胱癌患者总生存期(OS)较差相关,阐明其预后相关性。基因富集分析表明,SLC31A1可以影响代谢和铜相关过程,进一步强调其在膀胱癌中的作用。最后,我们探索了DrugBank数据库,以确定能够降低SLC31A1表达的潜在治疗药物.我们的发现揭示了六种重要的药物,有可能靶向SLC31A1作为治疗策略。结论:我们的全面调查强调SLC31A1是膀胱癌发展的有希望的生物标志物,programming,和治疗。
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