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采用 UPLC-MS/MS 方法检测正常个体、结直肠腺瘤或结直肠癌患者血清代谢产物特征。

Serum metabolite signatures in normal individuals and patients with colorectal adenoma or colorectal cancer using UPLC-MS/MS method.

机构信息

Chinese PLA General Hospital, No. 28, Fuxing Road Haidian District, Beijing 100853, China; Department of Gastroenterology, The Seventh Medical Center of Chinese PLA General Hospital, No. 5 Nanmencang, Dongcheng District, Beijing 100700, China.

Cancer Research Center, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, No. 9 Beiguan Street, Tongzhou District, Beijing 101149, China.

出版信息

J Proteomics. 2023 Jan 6;270:104741. doi: 10.1016/j.jprot.2022.104741. Epub 2022 Sep 26.

Abstract

Colorectal cancer (CRC) is one of the main causes of cancer-related deaths worldwide. Sporadic CRC develops from normal mucosa via adenoma to adenocarcinoma, which provides a long screening window for clinical detection. However, early diagnosis of sporadic colorectal adenoma (CRA) and CRC using serum metabolic screening remains unclear. The purpose of this study was to identify some promising signatures for distinguishing the different pathological metabolites of colorectal mucosal malignant transformation. A total of 238 endogenous metabolites were elected. We found that CRA and CRC patients had 72 and 73 different metabolites compared with healthy controls, respectively. There were 20 different metabolites between CRA and CRC patients. The potential metabolites of tumor growth (including patients with CRA and CRC) were found, such as A-d-glucose, D-mannose, N-acetyl-D-glucosamine, L-cystine, Sarcosine, TXB 2, 12-Hete, and chenodeoxycholic acid. Compared with CRA, 3,4,5-trimethoxybenzoic acid was significantly higher in CRC patients. There results prompt us to use the potential serum signatures to screen CRC as the novel strategy. Serum metabolite screening is useful for early detection of mucosal intestinal malignancy. We will further investigate the roles of these promising biomarkers during intestinal tumorigenesis in future. SIGNIFICANCE: CRC is one of the main causes of cancer-related deaths worldwide. Sporadic CRC develops from normal mucosa via adenomas to adenocarcinoma, which provides a long screening window for about 5-10 years. We adopt the metabolic analysis of extensive targeted metabolic technology. The main purpose of the metabolic group analysis is to detect and screen the different metabolites, thereby performing related functional prediction and analysis of the differential metabolites. In our study, 30 samples are selected, divided into 3 groups for metabolic analysis, and 238 metabolites are elected. In 238 metabolites, we find that CRA patients have 72 different metabolites compared with health control. Compared with health control, CRC have 73 different metabolites. Compared with CRA and CRC patients, there are 20 different metabolites. The annotation results of the significantly different metabolites are classified according to the KEGG pathway type. The potential metabolites of tumor growth stage (including patients with CRA and CRC) are found, such as A-d-glucose, D-mannose, N-acetyl-D-glucosamine, L-cystine, sarcosine, TXB 2, 12-Hete and chenodeoxycholic acid. Compared with CRA patients, CRC patients had significantly higher 3,4,5-trimethoxybenzoic acid level. It is prompted to use serum different metabolites to screen CRC to provide new possibilities.

摘要

结直肠癌(CRC)是全球癌症相关死亡的主要原因之一。散发性 CRC 由正常黏膜经腺瘤发展为腺癌,为临床检测提供了较长的筛查窗口。然而,利用血清代谢物筛查早期诊断散发性结直肠腺瘤(CRA)和 CRC 仍不清楚。本研究旨在确定一些有前途的特征,以区分结直肠黏膜恶性转化的不同病理代谢物。共选择了 238 种内源性代谢物。我们发现,与健康对照组相比,CRA 和 CRC 患者分别有 72 种和 73 种不同的代谢物。CRA 和 CRC 患者之间有 20 种不同的代谢物。发现了肿瘤生长的潜在代谢物(包括 CRA 和 CRC 患者),如 A-d-葡萄糖、D-甘露糖、N-乙酰-D-葡萄糖胺、L-胱氨酸、肌氨酸、血栓素 B2、12-HETE 和鹅去氧胆酸。与 CRA 相比,CRC 患者的 3,4,5-三甲氧基苯甲酸明显升高。这些结果提示我们使用潜在的血清特征来筛选 CRC 作为一种新的策略。血清代谢物筛查有助于早期发现黏膜肠道恶性肿瘤。我们将在未来进一步研究这些有前途的生物标志物在肠道肿瘤发生过程中的作用。意义:CRC 是全球癌症相关死亡的主要原因之一。散发性 CRC 由正常黏膜经腺瘤发展为腺癌,为大约 5-10 年的筛查提供了较长的窗口。我们采用广泛靶向代谢技术的代谢分析。代谢组分析的主要目的是检测和筛选不同的代谢物,从而对差异代谢物进行相关的功能预测和分析。在我们的研究中,选择了 30 个样本,分为 3 组进行代谢分析,选择了 238 种代谢物。在 238 种代谢物中,我们发现 CRA 患者与健康对照组相比有 72 种不同的代谢物。与健康对照组相比,CRC 有 73 种不同的代谢物。与 CRA 和 CRC 患者相比,有 20 种不同的代谢物。根据 KEGG 途径类型对差异显著的代谢物的注释结果进行分类。发现了肿瘤生长阶段的潜在代谢物(包括 CRA 和 CRC 患者),如 A-d-葡萄糖、D-甘露糖、N-乙酰-D-葡萄糖胺、L-胱氨酸、肌氨酸、血栓素 B2、12-HETE 和鹅去氧胆酸。与 CRA 患者相比,CRC 患者的 3,4,5-三甲氧基苯甲酸水平明显升高。提示利用血清不同代谢物筛查 CRC 以提供新的可能性。

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