晚期神经内分泌肿瘤（NETs）患者的综合血浆代谢组学特征。诊断及生物学相关性。

Comprehensive Plasma Metabolomic Profile of Patients with Advanced Neuroendocrine Tumors (NETs). Diagnostic and Biological Relevance.

作者信息

Soldevilla Beatriz, López-López Angeles, Lens-Pardo Alberto, Carretero-Puche Carlos, Lopez-Gonzalvez Angeles, La Salvia Anna, Gil-Calderon Beatriz, Riesco-Martinez Maria C, Espinosa-Olarte Paula, Sarmentero Jacinto, Rubio-Cuesta Beatriz, Rincón Raúl, Barbas Coral, Garcia-Carbonero Rocio

机构信息

Clinical and Translational Oncology Laboratory, Gastrointestinal Unit, i+12 Research Institute Hospital 12 de Octubre, 28041 Madrid, Spain.

Spanish National Cancer Research Center (CNIO), 28029 Madrid, Spain.

出版信息

Cancers (Basel). 2021 May 27;13(11):2634. doi: 10.3390/cancers13112634.

PURPOSE

High-throughput "-omic" technologies have enabled the detailed analysis of metabolic networks in several cancers, but NETs have not been explored to date. We aim to assess the metabolomic profile of NET patients to understand metabolic deregulation in these tumors and identify novel biomarkers with clinical potential.

METHODS

Plasma samples from 77 NETs and 68 controls were profiled by GC-MS, CE-MS and LC-MS untargeted metabolomics. OPLS-DA was performed to evaluate metabolomic differences. Related pathways were explored using Metaboanalyst 4.0. Finally, ROC and OPLS-DA analyses were performed to select metabolites with biomarker potential.

RESULTS

We identified 155 differential compounds between NETs and controls. We have detected an increase of bile acids, sugars, oxidized lipids and oxidized products from arachidonic acid and a decrease of carnitine levels in NETs. MPA/MSEA identified 32 enriched metabolic pathways in NETs related with the TCA cycle and amino acid metabolism. Finally, OPLS-DA and ROC analysis revealed 48 metabolites with diagnostic potential.

CONCLUSIONS

This study provides, for the first time, a comprehensive metabolic profile of NET patients and identifies a distinctive metabolic signature in plasma of potential clinical use. A reduced set of metabolites of high diagnostic accuracy has been identified. Additionally, new enriched metabolic pathways annotated may open innovative avenues of clinical research.

目的

高通量“组学”技术已能够对多种癌症中的代谢网络进行详细分析，但迄今为止尚未对神经内分泌肿瘤（NETs）进行探索。我们旨在评估NET患者的代谢组学特征，以了解这些肿瘤中的代谢失调情况，并确定具有临床潜力的新型生物标志物。

方法

通过气相色谱-质谱联用（GC-MS）、毛细管电泳-质谱联用（CE-MS）和液相色谱-质谱联用（LC-MS）非靶向代谢组学技术对77例NET患者和68例对照的血浆样本进行分析。采用正交偏最小二乘法判别分析（OPLS-DA）评估代谢组学差异。使用Metaboanalyst 4.0探索相关代谢途径。最后，进行受试者工作特征曲线（ROC）和OPLS-DA分析以选择具有生物标志物潜力的代谢物。

结果

我们确定了NET患者和对照之间的155种差异化合物。我们检测到NET患者中胆汁酸、糖类、氧化脂质以及花生四烯酸氧化产物增加，肉碱水平降低。多变量通路分析/多变量统计富集分析（MPA/MSEA）确定了NET中32条与三羧酸循环和氨基酸代谢相关的富集代谢途径。最后，OPLS-DA和ROC分析揭示了48种具有诊断潜力的代谢物。