Zhang Junbao, Zhang Zhihan, Liu Yuying, Hou Yanyi, Pang Ruifang, Wang Yuenan, Xu Ping
Department of Pulmonary and Critical Care Medicine, Peking University Shenzhen Hospital, Shenzhen, 518034, Guangdong Province, People's Republic of China.
Peking University Health Science Center, Beijing, China.
BMC Cancer. 2025 May 8;25(1):844. doi: 10.1186/s12885-025-14253-2.
Increasing pulmonary nodule presentations in lung adenocarcinoma patients reveal diagnostic limitations of CT-based invasiveness assessment. The critical unmet need lies in developing non-invasive biomarkers differentiating invasive adenocarcinoma from premalignant lesions and benign nodules, while characterizing metabolic trajectory from health to metastatic disease.
Untargeted metabolomics analyzed plasma samples from 102 subjects stratified into four cohorts: confirmed adenocarcinoma (n = 35), benign nodules (n = 22), precursor lesions (n = 24), and healthy controls (n = 21). Multivariate analysis identified discriminative metabolites for constructing an infiltration prediction model.
Three diagnostic groups exhibited distinct metabolic profiles. Hexaethylene glycol, tetraethylene glycol, and Met-Thr showed stage-dependent concentration gradients. Progressive malignancy correlated with elevated levels of 41 metabolites. An eight-metabolite panel achieved AUC 0.933 (0.873-0.994) in distinguishing precursors from early malignancies, sustained through internal validation (AUC 0.934, 0.905-0.966).
Met-Thr depletion inversely correlates with malignancy progression, while eight-metabolite signatures demonstrate diagnostic potential for preoperative infiltration assessment in nodular adenocarcinoma.
肺腺癌患者中肺结节表现的增加揭示了基于CT的侵袭性评估的诊断局限性。尚未满足的关键需求在于开发非侵入性生物标志物，以区分侵袭性腺癌与癌前病变和良性结节，同时描绘从健康到转移性疾病的代谢轨迹。
非靶向代谢组学分析了102名受试者的血浆样本，这些受试者被分为四个队列：确诊腺癌（n = 35）、良性结节（n = 22）、前驱病变（n = 24）和健康对照（n = 21）。多变量分析确定了用于构建浸润预测模型的判别性代谢物。
三个诊断组表现出不同的代谢谱。六甘醇、四甘醇和甲硫氨酸苏氨酸显示出阶段依赖性浓度梯度。恶性进展与41种代谢物水平升高相关。一个由八种代谢物组成的面板在区分前驱病变与早期恶性肿瘤方面的曲线下面积（AUC）为0.933（0.873 - 0.994），经内部验证后仍保持（AUC 0.934，0.905 - 0.966）。
甲硫氨酸苏氨酸的消耗与恶性进展呈负相关，而八种代谢物特征显示出对结节状腺癌术前浸润评估的诊断潜力。
