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18F标记BAY-588分子靶向肺腺癌预后标志物SLC2A1的计算模拟研究

Predictive Biomarker SLC2A1 in Lung Adenocarcinoma Targeted by 18F-BAY-588: A Computational Simulation Study

  • 摘要: 肺腺癌(Lung adenocarcinoma, LUAD)是一种发病率、致死率较高的疾病,目前针对肺腺癌的预后诊断的准确性和个体化水平有待进一步提高。基于生物信息学和正电子发射计算机断层成像技术(Positron Emission Tomography/Computed Tomography, PET/CT)建立预后模型和发掘靶向药物对该疾病的治疗具有重要意义。本研究采用Lasso-Cox算法对TCGA、GEO数据库中的肺腺癌转录组数据进行分析,筛选出与患者预后相关的基因,建立高性能的LUAD预后预测模型。该模型能够准确地区分高低风险患者,其一、三、五年生存率AUC值分别为0.821、0.693、0.701。基于该模型对ChEMBL数据库进行筛选,发现一种具有潜力的候选化合物BAY-588,对其进行18F放射性同位素标记的模拟计算,并揭示其可用于PET成像,为肺腺癌的诊断和治疗放射性药物的研发提供了科学证据。

     

    Abstract: Lung adenocarcinoma(LUAD) is a disease with high morbidity and mortality rates, underscoring the need for enhanced accuracy and personalization in prognostic diagnostics. The integration of bioinformatics with positron emission tomography/computed tomography(PET/CT) presents substantial potential for the development of prognostic models and the identification of targeted therapeutics. In this study, we employed the Lasso-Cox algorithm to analyze LUAD transcriptomic data from the TCGA and GEO databases, successfully identifying prognosis-associated genes and constructing a high-performance prognostic prediction model. This model demonstrated robust stratification of high- and low-risk patients, achieving AUC values of 0.821, 0.693, and 0.701 for 1-, 3-, and 5-year survival rates, respectively. Subsequent virtual screening of the ChEMBL database using the model identified BAY-588 as a promising candidate compound. Computational simulations of 18F radiolabeling revealed its potential utility in PET imaging, providing scientific evidence for the development of theranostic radiopharmaceuticals targeting LUAD.

     

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