胰腺导管腺癌分子图谱中的关键基因和通路:一项生物信息学和机器学习研究。

IF 2.6 4区 生物学 Q2 BIOLOGY
Sinan Eyuboglu , Semih Alpsoy , Vladimir N. Uversky , Orkid Coskuner-Weber
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引用次数: 0

摘要

胰腺导管腺癌(PDAC)因其侵袭性强、预后不良、五年存活率明显偏低而被公认,这凸显了对早期检测方法和更有效治疗方法的迫切需要。这项研究对 PDAC 的分子机制进行了严格研究,重点是确定可能具有治疗意义和预后价值的关键基因和通路。通过构建蛋白-蛋白相互作用(PPI)网络和检测差异表达基因(DEGs),研究发现了CDK1、KIF11和BUB1等关键枢纽基因,证明了它们在PDAC发病机制中的重要作用。值得注意的是,这些基因的失调在各种癌症中都是一致的,因此它们被认为是各种癌症疗法的潜在靶点。这项研究还揭示了编码内在紊乱蛋白的重要基因,特别是 GPRC5A 和 KRT7,为治疗干预揭示了前景广阔的新途径。利用关键遗传标记作为数据集,先进的机器学习技术对 PDAC 患者进行了高精度分类。支持向量机(SVM)模型利用枢纽基因实现了 91% 的灵敏度和 85% 的特异性,而随机森林(RandomForest)模型则实现了 91% 的灵敏度和 92.5% 的特异性。最重要的是,当将鉴定出的基因与TCGA-PAAD临床数据集进行交叉比对时,发现了这些基因与患者存活率的切实相关性,从而增强了这些基因作为预后生物标志物的潜力及其作为治疗干预靶点的可行性。这项研究的发现有力地证明了分子分析在增进人们对 PDAC 的了解以及推动人们寻求更有效的诊断和治疗策略方面的价值。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Key genes and pathways in the molecular landscape of pancreatic ductal adenocarcinoma: A bioinformatics and machine learning study
Pancreatic ductal adenocarcinoma (PDAC) is recognized for its aggressive nature, dismal prognosis, and a notably low five-year survival rate, underscoring the critical need for early detection methods and more effective therapeutic approaches. This research rigorously investigates the molecular mechanisms underlying PDAC, with a focus on the identification of pivotal genes and pathways that may hold therapeutic relevance and prognostic value. Through the construction of a protein-protein interaction (PPI) network and the examination of differentially expressed genes (DEGs), the study uncovers key hub genes such as CDK1, KIF11, and BUB1, demonstrating their substantial role in the pathogenesis of PDAC. Notably, the dysregulation of these genes is consistent across a spectrum of cancers, positing them as potential targets for wide-ranging cancer therapeutics. This study also brings to the fore significant genes encoding intrinsically disordered proteins, in particular GPRC5A and KRT7, unveiling promising new pathways for therapeutic intervention. Advanced machine learning techniques were harnessed to classify PDAC patients with high accuracy, utilizing the key genetic markers as a dataset. The Support Vector Machine (SVM) model leveraged the hub genes to achieve a sensitivity of 91 % and a specificity of 85 %, while the RandomForest model notched a sensitivity of 91 % and specificity of 92.5 %. Crucially, when the identified genes were cross-referenced with TCGA-PAAD clinical datasets, a tangible correlation with patient survival rates was discovered, reinforcing the potential of these genes as prognostic biomarkers and their viability as targets for therapeutic intervention. This study's findings serve as a potent testament to the value of molecular analysis in enhancing the understanding of PDAC and in advancing the pursuit for more effective diagnostic and treatment strategies.
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来源期刊
Computational Biology and Chemistry
Computational Biology and Chemistry 生物-计算机:跨学科应用
CiteScore
6.10
自引率
3.20%
发文量
142
审稿时长
24 days
期刊介绍: Computational Biology and Chemistry publishes original research papers and review articles in all areas of computational life sciences. High quality research contributions with a major computational component in the areas of nucleic acid and protein sequence research, molecular evolution, molecular genetics (functional genomics and proteomics), theory and practice of either biology-specific or chemical-biology-specific modeling, and structural biology of nucleic acids and proteins are particularly welcome. Exceptionally high quality research work in bioinformatics, systems biology, ecology, computational pharmacology, metabolism, biomedical engineering, epidemiology, and statistical genetics will also be considered. Given their inherent uncertainty, protein modeling and molecular docking studies should be thoroughly validated. In the absence of experimental results for validation, the use of molecular dynamics simulations along with detailed free energy calculations, for example, should be used as complementary techniques to support the major conclusions. Submissions of premature modeling exercises without additional biological insights will not be considered. Review articles will generally be commissioned by the editors and should not be submitted to the journal without explicit invitation. However prospective authors are welcome to send a brief (one to three pages) synopsis, which will be evaluated by the editors.
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