Background/Objectives: Pulmonary neuroendocrine neoplasms (NENs) account for 20% of malignant lung tumors. Their management is challenging due to their diverse clinical features and aggressive nature. Currently, metabolomics offers a range of potential cancer biomarkers for diagnosis, monitoring tumor progression, and assessing therapeutic response. However, a specific metabolomic profile for early diagnosis of lung NENs has yet to be identified. This study aims to identify specific metabolomic profiles that can serve as biomarkers for early diagnosis of lung NENs. Methods: We measured 153 metabolites using liquid chromatography combined with mass spectrometry (LC-MS) in the plasma of 120 NEN patients and compared them with those of 71 healthy individuals. Additionally, we compared these profiles with those of 466 patients with non-small-cell lung cancers (NSCLCs) to ensure clinical relevance. Results: We identified 21 metabolites with consistently altered plasma concentrations in NENs. Compared to healthy controls, 18 metabolites were specific to carcinoid tumors, 5 to small-cell lung carcinomas (SCLCs), and 10 to large-cell neuroendocrine carcinomas (LCNECs). These findings revealed alterations in various metabolic pathways, such as fatty acid biosynthesis and beta-oxidation, the Warburg effect, and the citric acid cycle. Conclusions: Our study identified biomarker metabolites in the plasma of patients with each subtype of lung NENs and demonstrated significant alterations in several metabolic pathways. These metabolomic profiles could potentially serve as biomarkers for early diagnosis and better management of lung NENs.
**背景/目的：** 肺神经内分泌肿瘤占恶性肺肿瘤的20%。由于其多样的临床特征和侵袭性，其治疗具有挑战性。目前，代谢组学为癌症的诊断、监测肿瘤进展和评估治疗反应提供了一系列潜在的生物标志物。然而，用于肺神经内分泌肿瘤早期诊断的特异性代谢组学特征谱尚未确定。本研究旨在识别可作为肺神经内分泌肿瘤早期诊断生物标志物的特异性代谢组学特征谱。 **方法：** 我们使用液相色谱-质谱联用技术，测量了120名神经内分泌肿瘤患者血浆中的153种代谢物，并与71名健康个体的血浆代谢物进行了比较。此外，为确保临床相关性，我们将这些特征谱与466名非小细胞肺癌患者的特征谱进行了比较。 **结果：** 我们鉴定出21种在神经内分泌肿瘤患者血浆中浓度持续改变的代谢物。与健康对照组相比，18种代谢物为类癌特异性，5种为小细胞肺癌特异性，10种为大细胞神经内分泌癌特异性。这些发现揭示了多种代谢途径的改变，例如脂肪酸生物合成与β-氧化、瓦博格效应以及柠檬酸循环。 **结论：** 我们的研究识别了肺神经内分泌肿瘤各亚型患者血浆中的生物标志物代谢物，并揭示了几种代谢途径的显著改变。这些代谢组学特征谱有望作为生物标志物，用于肺神经内分泌肿瘤的早期诊断和更好的临床管理。
肿瘤(癌症)患者之家