Tao Xuetong, Wang Haiyan, Qu Jiaxiang, Chen Zixiang, Wu Yaping, Chen Ruohua, Liu Jianjun, Zhang Na, Zheng Hairong, Liang Dong, Wang Meiyun, Hu Zhanli
Lauterbur Research Center for Biomedical Imaging, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
Key Laboratory of Biomedical Imaging Science and System, State Key Laboratory of Biomedical Imaging Science and System, Chinese Academy of Sciences, Shenzhen, 518055, China.
Eur J Nucl Med Mol Imaging. 2025 Jun 3. doi: 10.1007/s00259-025-07371-3.
PURPOSE: Cancer is increasingly recognized not just as a localized disease but as a systemic condition with profound impacts on metabolism at both cellular and whole-body levels. This study seeks to unveil the systemic metabolic disruptions in early-stage, untreated lung cancer patients, specifically adenocarcinoma (ADC) and squamous cell carcinoma (SqCC), using a novel network-based approach with total-body static and dynamic PET/CT imaging. By analyzing inter-organ metabolic dependencies, we aim to uncover how lung cancer induces whole-body metabolic reprogramming, providing insights into potential biomarkers for monitoring disease progression and treatment response. METHODS: This retrospective study included 32 early-stage untreated lung cancer patients and 20 healthy volunteers. Static and dynamic total-body PET/CT scans were performed to assess glucose consumption across the body. Twenty-five regions of interest (ROIs) representing major organs were selected, and metabolic status was quantified using the average SUV and Ki values for each ROI. Inter-organ metabolic dependencies were quantified using mutual information (MI), which measures the amount of shared information between two variables, capturing both linear and nonlinear relationships, followed by Bonferroni correction to control for multiple comparisons. Population-level metabolic networks were constructed to visualize alterations in interregional connectivity for ADC, SqCC, and healthy cohorts. Furthermore, to capture personalized metabolic deviations, individual networks were constructed for each cancer patient. RESULTS: The analysis revealed distinct metabolic network patterns in ADC and SqCC patients compared to healthy controls. ADC patients exhibited selective enhancements in metabolic connectivity, particularly between the central nervous system and peripheral organs such as the adrenal glands and pancreas, suggesting activation of compensatory neuroendocrine mechanisms. In contrast, SqCC patients showed widespread reductions in metabolic connectivity, indicative of a systemic metabolic breakdown associated with disease progression. Individual-level network analysis highlighted personalized metabolic deviations. CONCLUSION: Total-body PET/CT combined with network-based methods facilitates the quantitative visualization of systemic metabolic alterations in lung cancer. ADC and SqCC exhibit unique metabolic profiles that may offer insights into disease progression and the identification of potential biomarkers for therapeutic monitoring. Larger, longitudinal studies are required to validate these findings and further explore their clinical relevance for early diagnosis and treatment stratification in lung cancer. CLINICAL TRIAL NUMBER: Not applicable.
目的:癌症越来越被认为不仅是一种局部疾病,而且是一种对细胞和全身水平的代谢都有深远影响的全身性疾病。本研究旨在使用基于新型网络的全身静态和动态PET/CT成像方法,揭示早期未经治疗的肺癌患者,特别是腺癌(ADC)和鳞状细胞癌(SqCC)患者的全身代谢紊乱情况。通过分析器官间的代谢依赖性,我们旨在揭示肺癌如何诱导全身代谢重编程,为监测疾病进展和治疗反应的潜在生物标志物提供见解。 方法:这项回顾性研究包括32例早期未经治疗的肺癌患者和20名健康志愿者。进行全身静态和动态PET/CT扫描以评估全身的葡萄糖消耗情况。选择代表主要器官的25个感兴趣区域(ROI),并使用每个ROI的平均SUV和Ki值对代谢状态进行量化。使用互信息(MI)对器官间的代谢依赖性进行量化,互信息用于测量两个变量之间共享信息的量,可捕捉线性和非线性关系,随后进行Bonferroni校正以控制多重比较。构建群体水平的代谢网络,以可视化ADC、SqCC和健康队列中区域间连接性的变化。此外,为了捕捉个性化的代谢偏差,为每位癌症患者构建个体网络。 结果:分析显示,与健康对照组相比,ADC和SqCC患者具有独特的代谢网络模式。ADC患者在代谢连接性方面表现出选择性增强,特别是在中枢神经系统与肾上腺和胰腺等外周器官之间,这表明代偿性神经内分泌机制被激活。相比之下,SqCC患者的代谢连接性普遍降低,这表明与疾病进展相关的全身代谢崩溃。个体水平的网络分析突出了个性化的代谢偏差。 结论:全身PET/CT结合基于网络的方法有助于对肺癌患者的全身代谢改变进行定量可视化。ADC和SqCC表现出独特的代谢特征,这可能为疾病进展以及治疗监测潜在生物标志物的识别提供见解。需要进行更大规模的纵向研究来验证这些发现,并进一步探索它们在肺癌早期诊断和治疗分层中的临床相关性。 临床试验编号:不适用。
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