Laboratory of Hematology Center, The First Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.
Department of Colorectal Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, 150086, China.
Metabolomics. 2020 Feb 24;16(3):29. doi: 10.1007/s11306-020-1651-x.
Colorectal cancer (CRC) remains an incurable disease. Previous metabolomic studies show that metabolic signatures in plasma distinguish CRC patients from healthy controls. Chronic enteritis (CE) represents a risk factor for CRC, with a 20 fold greater incidence than in healthy individuals. However, no studies have performed metabolomic profiling to investigate CRC biomarkers in CE.
Our aims were to identify metabolomic signatures in CRC and CE and to search for blood-derived metabolite biomarkers distinguishing CRC from CE, especially early-stage biomarkers.
In this case-control study, 612 subjects were prospectively recruited between May 2015 and May 2016, and including 539 CRC patients (stage I, 102 cases; stage II, 259 cases; stage III, 178 cases) and 73 CE patients. Untargeted metabolomics was performed to identify CRC-related metabolic signatures in CE.
Five pathways were significantly enriched based on 153 differential metabolites between CRC and CE. 16 biomarkers were identified for diagnosis of CRC from CE and for guiding CRC staging. The AUC value for CRC diagnosis in the external validation set was 0.85. Good diagnostic performances were also achieved for early-stage CRC (stage I and stage II), with an AUC value of 0.84. The biomarker panel could also stage CRC patients, with an AUC of 0.72 distinguishing stage I from stage II CRC and AUC of 0.74 distinguishing stage II from stage III CRC.
The identified metabolic biomarkers exhibit promising properties for CRC monitoring in CE patients and are superior to commonly used clinical biomarkers (CEA and CA19-9).
结直肠癌(CRC)仍然是一种无法治愈的疾病。先前的代谢组学研究表明,血浆中的代谢特征可将 CRC 患者与健康对照者区分开来。慢性肠炎(CE)是 CRC 的一个危险因素,其发病率比健康个体高 20 倍。然而,尚无研究对 CE 中的 CRC 生物标志物进行代谢组学分析。
我们的目的是确定 CRC 和 CE 中的代谢特征,并寻找可将 CRC 与 CE 区分开的血液衍生代谢物生物标志物,特别是早期生物标志物。
在这项病例对照研究中,我们于 2015 年 5 月至 2016 年 5 月期间前瞻性招募了 612 名受试者,其中包括 539 名 CRC 患者(I 期,102 例;II 期,259 例;III 期,178 例)和 73 名 CE 患者。我们进行了非靶向代谢组学分析,以确定 CE 中与 CRC 相关的代谢特征。
基于 CRC 和 CE 之间的 153 种差异代谢物,发现了 5 条显著富集的途径。我们鉴定出了 16 种用于从 CE 诊断 CRC 并指导 CRC 分期的生物标志物。在外部验证集中,CRC 诊断的 AUC 值为 0.85。对于早期 CRC(I 期和 II 期),也取得了良好的诊断性能,AUC 值为 0.84。该生物标志物谱还可对 CRC 患者进行分期,区分 I 期和 II 期 CRC 的 AUC 值为 0.72,区分 II 期和 III 期 CRC 的 AUC 值为 0.74。
所鉴定的代谢生物标志物在 CE 患者的 CRC 监测中具有良好的应用前景,优于常用的临床生物标志物(CEA 和 CA19-9)。