Boullier Clémence, Lamaze Fabien C, Haince Jean-François, Bux Rashid Ahmed, Orain Michèle, Zheng Jiamin, Zhang Lun, Wishart David S, Bossé Yohan, Manem Venkata S K, Joubert Philippe
Centre de Recherche de l'institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ), Quebec City, QC G1V 4G5, Canada.
Faculty of Medicine, Laval University, Quebec City, QC G1V 0A6, Canada.
Cancers (Basel). 2024 Sep 17;16(18):3179. doi: 10.3390/cancers16183179.
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.
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.
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.
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（NENs）占恶性肺肿瘤的20%。由于其多样的临床特征和侵袭性，其治疗颇具挑战性。目前，代谢组学为癌症诊断、监测肿瘤进展及评估治疗反应提供了一系列潜在的生物标志物。然而，尚未确定用于早期诊断肺NENs的特定代谢组学特征。本研究旨在识别可作为肺NENs早期诊断生物标志物的特定代谢组学特征。
我们使用液相色谱-质谱联用（LC-MS）技术测定了120例NEN患者血浆中的153种代谢物，并将其与71名健康个体的代谢物进行比较。此外，我们将这些特征与466例非小细胞肺癌（NSCLCs）患者的特征进行比较，以确保临床相关性。
我们在NENs中鉴定出21种血浆浓度持续改变的代谢物。与健康对照相比，18种代谢物对类癌肿瘤具有特异性，5种对小细胞肺癌（SCLCs）具有特异性，10种对大细胞神经内分泌癌（LCNECs）具有特异性。这些发现揭示了各种代谢途径的改变，如脂肪酸生物合成和β-氧化、瓦伯格效应和柠檬酸循环。
我们的研究在肺NENs各亚型患者的血浆中鉴定出了生物标志物代谢物，并证明了几种代谢途径的显著改变。这些代谢组学特征可能作为肺NENs早期诊断和更好管理的生物标志物。
