| 贺晓兰,马辰莺,徐晓婷.宫颈癌放射治疗患者代谢产物表达与急性放射性肠炎相关性的研究[J].中华放射医学与防护杂志,2020,40(1):1-10 |
| 宫颈癌放射治疗患者代谢产物表达与急性放射性肠炎相关性的研究 |
| Correlation between the expression of metabolites and acute radiation enteritis in patients with cervical cancer |
| 投稿时间：2019-07-17 |
| DOI：10.3760/cma.j.issn.0254-5098.2020.01.001 |
| 中文关键词: 宫颈癌 代谢组学 急性放射性肠炎 |
| 英文关键词:Cervical cancer Metabolomics Radiation-induced acute intestinal symptoms |
| 基金项目:国家自然科学基金（81602792） |
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| 摘要点击次数: 2435 |
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| 中文摘要: |
| 目的 在探讨宫颈癌患者放疗过程中粪便样本中代谢产物的表达变化与急性放射性肠炎发生的相关性。方法 选取2017年9月至2018年6月在苏州大学附属第一医院接受宫颈癌放疗的患者51例（其中1名患者因入组后不能按要求留存有效标本而剔除，实际共50例），收集患者放疗期间4个时间点的粪便样本，即放疗开始、放疗2周、放疗4周、放疗结束，共计200个，采用液相色谱-质谱（LC-MS）的非靶向代谢组学方法检测。采用偏最小二乘法-判别分析（PLS-DA），凝聚层次聚类分析等统计方法鉴定粪便中代谢产物的变化趋势。结果 通过LC-MS的非靶向代谢组学分析，共检测到5 770个代谢峰，鉴定出121个显著失调的差异代谢产物，其中77个代谢产物表达上调，44个代谢产物表达下调。有19个差异代谢产物在放疗4个时间点发生显著变化，包括1-甲基黄嘌呤、亚油酸、5-氨基戊酸、苯乙胺、苯乙烯、N-乙酰谷氨酸、19-去甲睾酮、4-乙酰氨基丁酸、N-乙酰-L-苯丙氨酸、大豆苷元、胆酸、花生四烯酸、甲蓝氨酸、N-甲酰-L-蛋氨酸、槲皮苷，苯丙氨酸、葡糖酸、蜜二糖及α-CMBHC。共筛选出4个代谢通路与放射性肠炎的发生有关（Pathway imPact >0.1），分别为苯丙氨酸酪氨酸代谢通路、烟酸和烟酰胺代谢通路、亚油酸代谢通路、赖氨酸降解代谢通路。结论 宫颈癌患者放疗后粪便中代谢产物发生明显改变。随着放疗剂量的增加，粪便上清中的差异代谢产物表达发生不同程度的上调或下调，为急性放射性肠炎的预测提供了新的思路和方法。 |
| 英文摘要: |
| Objective To investigate the relationship between the metabolites in the fecal samples from cervical cancer patients and radiation-induced acute intestinal symptoms during radiotherapy. Methods A total of 51 cervical cancer patients who received radiotherapy in our hospital from September 2017 to June 2018 were enrolled. One patient was excluded due to efficiant sample failure, so a total of 50 patients were included in the study. Totally 200 fecal samples were collected at four time points, i.e. before radiotherapy, 2 weeks post radiotherapy starting, 4 weeks post radiotherapy starting and end of radiotherapy. These fecal samples were analyzed by non-targeted metabolomics using liquid chromatography-mass spectrometry (LC-MS). Data were analyzed with statistical method including partial least squares-discriminant analysis (PLS-DA), agglomerate hierarchical clustering to investigate the trend of metabolites expression in feces. Results A total of 5 770 metabolic peaks were detected and 121 biomarkers were identified, of which 77 biomarkers were up-regulated and 44 biomarkers were down-regulated. Nineteen biomarkers were significantly changed at four time points after radiotherapy, including 1-methylxanthine, linoleic acid, 5-aminopentanoic acid, phenethylamine, styrene, N-acetylglutamate, nandrolone, 4-acetylaminobutyric acid, N-acetyl-L-phenylalanine, daidzein, cholic acid, arachidonic acid, methyl leucine, N-formyl-L-methionine, quercetin, phenylalanine, gluconic acid, melibiose and α-CMBHC. Four metabolic pathways of phenylalanine tyrosine, niacin and nicotinamide, linoleic acid and lysine degradation (Pathway imPact >0.1) were found to be related to acute radiation enteritis. Conclusions The metabolites in the feces of cervical cancer patients change significantly during radiotherapy, and some biomarkers in the fecal supernatant are up- or down-regulated to varying degrees as doses increase, which provides new ideas and method for the prediction of acute radiation enteritis. |
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