采用靶向代谢组学分析鉴定子宫内膜癌的新型诊断生物标志物。

Identification of novel diagnostic biomarkers in endometrial cancer using targeted metabolomic profiling.

机构信息

Division of Gynaecology and Perinatology, University Medical Centre Maribor, Maribor, Slovenia; Faculty of Medicine, University of Maribor, Maribor, Slovenia.

Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia; Universal Diagnostics, S.L. Centre of Research Technology and Innovation, University of Seville, Seville, Spain.

出版信息

Adv Med Sci. 2021 Mar;66(1):46-51. doi: 10.1016/j.advms.2020.12.001. Epub 2020 Dec 24.

DOI:10.1016/j.advms.2020.12.001

PMID:33360772

Abstract

PURPOSE

Endometrial cancer (EC) is the most common gynecological malignancy with high disease burden especially in advanced stages of the disease. Our study investigated the metabolomic profile of EC patient's serum with the aim of identifying novel diagnostic biomarkers that could be used especially in early disease detection.

MATERIAL AND METHODS

Using targeted metabolomic serum profiling based on HPLC-TQ/MS, women with EC (n = 15) and controls (n = 21) were examined for 232 endogenous metabolites.

RESULTS

Top performing biomarkers included ceramides, acylcarnitines and 1-methyl adenosine. Top 4 biomarkers combined achieved 94% sensitivity with 75% specificity with AUC 92.5% (CI 90.5-94.5%). Individual markers also provided significant predictive values: C16-ceramide achieved sensitivity 73%, specificity 81%, AUC 0.83, C22-ceramide sensitivity 67%, specificity 81%, AUC 0.77, hydroxyhexadecenoylcarnitine sensitivity 60%, specificity 96%, AUC 0.76 and 1-methyladenosine sensitivity 67%, specificity 81%, AUC 0.75. The individual markers, however, did not reach the high sensitivity and specificity of the 4-biomarker combination.

CONCLUSIONS

Using mass spectrometry targeted metabolomic profiling, ceramides, acylcarnitines and 1-methyladenosine were identified as potential diagnostic biomarkers for EC. Additionally, these identified metabolites may provide additional insight into cancer cell metabolism.

摘要

目的

子宫内膜癌（EC）是最常见的妇科恶性肿瘤，尤其是在疾病晚期，其疾病负担很高。我们的研究旨在通过检测 EC 患者血清的代谢组学特征，寻找新的诊断生物标志物，尤其是在早期疾病检测中。

材料与方法

采用基于 HPLC-TQ/MS 的靶向代谢组学血清分析方法，对 15 例 EC 患者和 21 例对照者进行 232 种内源性代谢物检测。

结果

表现最好的生物标志物包括神经酰胺、酰基肉碱和 1-甲基腺苷。前 4 个标志物联合检测的敏感性为 94%，特异性为 75%，AUC 为 92.5%（90.5-94.5%）。单个标志物也具有显著的预测价值：C16-神经酰胺的敏感性为 73%，特异性为 81%，AUC 为 0.83；C22-神经酰胺的敏感性为 67%，特异性为 81%，AUC 为 0.77；羟基十六烯酰肉碱的敏感性为 60%，特异性为 96%，AUC 为 0.76；1-甲基腺苷的敏感性为 67%，特异性为 81%，AUC 为 0.75。然而，这些单个标志物并未达到 4 个标志物联合检测的高敏感性和特异性。