肺腺癌进展的高分辨率循环代谢图谱支持早期准确诊断
A high-resolution circulating metabolic atlas of lung adenocarcinoma progression supports early and accurate diagnosis.
作者
作者单位
- Department of Clinical Laboratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P.R. China; Shanghai Key Laboratory of Thoracic Tumor Biotherapy, Shanghai 200030, P.R. China; State Key Laboratory for Oncogenes and Related Genes, School of Biomedical Engineering, Institute of Medical Robotics and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, P.R. China.
- School of Public Health, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, P.R. China.
- Department of Surgical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, P.R. China.
- Department of Clinical Laboratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P.R. China.
- Department of Clinical Laboratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P.R. China; Shanghai Key Laboratory of Thoracic Tumor Biotherapy, Shanghai 200030, P.R. China.
- State Key Laboratory for Oncogenes and Related Genes, School of Biomedical Engineering, Institute of Medical Robotics and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, P.R. China.
- Department of Surgery, UT Southwestern Medical Center, Dallas, TX 75390, USA.
- Department of Clinical Laboratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P.R. China; Shanghai Key Laboratory of Thoracic Tumor Biotherapy, Shanghai 200030, P.R. China. Electronic address: jiayi.wang@sjtu.edu.cn.
- State Key Laboratory for Oncogenes and Related Genes, School of Biomedical Engineering, Institute of Medical Robotics and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, P.R. China. Electronic address: k.qian@sjtu.edu.cn.
- Department of Surgery, UT Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: daolin.tang@utsouthwestern.edu.
- Department of Clinical Laboratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P.R. China; Shanghai Key Laboratory of Thoracic Tumor Biotherapy, Shanghai 200030, P.R. China. Electronic address: linhuang@shsmu.edu.cn.
摘要
中文
肺腺癌（LUAD）的早期诊断，尤其是原位腺癌（AIS）阶段，对根治性治疗至关重要。基于血液的代谢进展分析提供了肿瘤发生的系统视图，可实现稳健、无创的早期检测。为此，我们使用超快纳米颗粒增强质谱平台，对来自以女性、不吸烟为主的中国队列的2,836份血清样本（覆盖正常肺至浸润性癌）进行了分析。这一整合的回顾性和前瞻性队列设计能够构建全面的代谢图谱，揭示在浸润前阶段出现并随组织学严重程度进展的保守代谢扰动。在这些轨迹的指导下，我们开发了一种十代谢物诊断检测方法，其性能在独立队列中可重复（总体曲线下面积0.900；浸润前疾病0.860）。值得注意的是，在调整人口统计学和生活方式混杂因素后，检测效能保持一致。这些发现确定代谢重编程为LUAD的早期标志，具有在人群水平早期检测中的潜在应用价值。
English
Early diagnosis of lung adenocarcinoma (LUAD), particularly at the adenocarcinoma in situ (AIS) stage, is critical for curative intervention. Profiling blood-based metabolic progression offers a systemic view of tumorigenesis to enable robust, noninvasive early detection. To achieve this, we profile 2,836 serum samples from predominantly female, never-smoking Chinese cohorts spanning normal lung to invasive carcinoma using an ultrafast nanoparticle-enhanced mass spectrometry platform. This integrated retrospective and prospective cohort design enables the construction of a comprehensive metabolic atlas, revealing conserved metabolic perturbations that arise at the pre-invasive stage and progress with histologic severity. Guided by these trajectories, we develop a ten-metabolite diagnostic assay that demonstrates reproducible performance across independent cohorts (area under the curve 0.900 for overall; 0.860 for pre-invasive disease). Notably, assay efficacy remains consistent after adjusting for demographic and lifestyle confounders. These findings identify metabolic rewiring as an early hallmark of LUAD, with potential utility in population-level early detection.
分类与指标
- 研究类型
- 基础研究
- 病种
- 肺癌
- JCR 分区
- Q1
- 影响因子
- 45.1
- 新锐分区
- 1区