Metabolomic mechanisms for the clinical phenomes of spleen deficiency and dampness-heat syndrome and dampness-heat accumulation syndrome associated with colorectal cancer

TIAN Yuan; YANG Zhongming; DU Xin; HUANG Jin; YE Lingyu Linda; DUAN Dayue Darrel

doi:10.3969/j.issn.1006-2157.2023.12.013

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Metabolomic mechanisms for the clinical phenomes of spleen deficiency and dampness-heat syndrome and dampness-heat accumulation syndrome associated with colorectal cancer

Experimental Studies | 更新时间：2024-01-03

- Metabolomic mechanisms for the clinical phenomes of spleen deficiency and dampness-heat syndrome and dampness-heat accumulation syndrome associated with colorectal cancer
- Journal of Beijing University of Traditional Chinese Medicine Vol. 46, Issue 12, Pages: 1728-1741(2023)
- 作者机构：
  
  1.西南医科大学附属中医医院　中医药表型组学研究中心　泸州　646000
  2.西南医科大学中西医结合学院
  3.四川省肿瘤医院中西医结合科
  4.西南医科大学附属中医医院肿瘤科
- 作者简介：
  
  Prof.DUAN Dayue Darrel, Doctoral Supervisor. Center for Phenomics of Traditional Chinese Medicine, and the Affiliated TCM Hospital of Southwest Medical University, No. 182 Chunhui Road, Longmatan District, Luzhou 646000.E-mail: dduan@swmu.edu.cn
- 基金信息：
  
  Evidence-based Capacity Building Project of Traditional Chinese Medicine(2019XZZX-ZL005);Luzhou Municipal People's Government and Southwest Medical University High-level Talents(2019LZXNYD-P01DUAN);Science and Technology Strategic Cooperation Project of Luzhou Municipal People's Government and Southwest Medical University(2018LZXNYD-ZK37)
- DOI：10.3969/j.issn.1006-2157.2023.12.013
  CLC： R273
- Received：27 March 2023，
  
  Online First：14 August 2023，
  
  Published：30 December 2023
- 稿件说明：
移动端阅览
TIAN Yuan, YANG Zhongming, DU Xin, et al. Metabolomic mechanisms for the clinical phenomes of spleen deficiency and dampness-heat syndrome and dampness-heat accumulation syndrome associated with colorectal cancer[J]. Journal of Beijing University of Traditional Chinese Medicine, 2023, 46(12): 1728-1741.
DOI：

TIAN Yuan, YANG Zhongming, DU Xin, et al. Metabolomic mechanisms for the clinical phenomes of spleen deficiency and dampness-heat syndrome and dampness-heat accumulation syndrome associated with colorectal cancer[J]. Journal of Beijing University of Traditional Chinese Medicine, 2023, 46(12): 1728-1741. DOI： 10.3969/j.issn.1006-2157.2023.12.013.

摘要

目的

阐明大肠癌脾虚湿热证表型组和湿热蕴结证表型组的代谢组学机制。

方法

2021年3月—2021年10月于西南医科大学附属中医医院招募大肠癌脾虚湿热证患者68例、湿热蕴结证患者58例，同时纳入于此进行体检的健康平和质人员62名。建立脾虚湿热证表型组、湿热蕴结证表型组和健康平和质表型组队列，以超高液相色谱和质谱联用技术对各队列血清代谢物进行分离鉴定，并进行主成分分析(PCA)、正交偏最小二乘判别分析法(OLPS-DA)分析及生物信息学分析。

结果

与健康平和质表型组相比，脾虚湿热证表型组有胍基乙酸下调，亚氨甲基谷氨酸、咪唑乙酸、脱氧尿苷、胞苷、假尿苷、鸟氨酸、

－乙酰鸟氨酸、5－羟吲哚乙酸、胆色素原、琥珀酸半醛、甜醇表达上调等12种差异代谢，涉及能量代谢异常为主的7条代谢途径；湿热蕴结证表型组有脱氧尿苷、胞苷、胆色素原、花生酸、前列腺素B

、异柠檬酸、古洛糖酸表达上调，胍基乙酸、尿苷、羟脯氨酸、吡咯－2－羧酸、腺苷、5，6－DHET、8，9－DiHETrE、9，10－DHOME、亚油酸、羟基丙酮酸表达下调等17种差异代谢，涉及脂类代谢和三羧酸循环异常为主的9条代谢途径；脾虚湿热证表型组与湿热蕴结证表型组存在4个相同特征性代谢物(胍基乙酸、脱氧尿苷、胞苷、胆色素原)差异。

结论

这些结果揭示了形成大肠癌脾虚湿热证和湿热蕴结证两个常见临床表型组的代谢组学机制，并为中医辨证和诊治提供临床表型组的循证依据和特异性代谢组学客观依据。

Abstract

Objective

To elucidate the metabolomic mechanisms for the clinical phenomes of spleen deficiency and dampness-heat syndrome (PXSR) and the dampness-heat accumulation syndrome (SRYJ) associated with colorectal cancer (CRC).

Methods

From March 2021 to October 2021

A total of 68 patients with spleen deficiency and dampness-heat syndrome and 58 patients with dampness-heat accumulation syndrome of colorectal cancer were recruited in the Affiliated Hospital of Traditional Chinese Medicine of Southwest Medical University

and 62 healthy control with balanced constitution personnel who underwent physical examination here. Cohorts were established for PXSR phenome (PXSRP)

SRYJ phenome (SRYJP)

and healthy control with balanced constitution (BC). Serum metabolites were isolated and identified by non-targeted metabolomics and ultra-high liquid chromatography and mass spectrometry (UHPLC-QE-MS); the results were further analyzed by principal component analysis (PCA)

Orthogonal partial least squares discriminant analysis (OLPS-DA) analysis and bioinformatics analysis.

Results

Compared with Group BC

Group PXSRP had 12 metabolite differences

including downregulation of guanidoacetic acid

and upregulation of formiminoglat-amic acid

imidazoleacetic acid

deoxyuridine

cytidine

pseudouridine

ornithine

N-acetylornithine

5-hydroxyindoleacetic acid

porphobilinogen

succinic acid semialdehyde

and galactitol.7 metabolic pathways were involved

mainly involving abnormal energy metabolism. Group SRYJP had 17 metabolite differences

including upregulation of deoxyuridine

cytidine

porphobilinogen

arachidonic acid

prostaglandin B2

isocitric acid

L-gulonolactone

and downregulation of guanidoacetic acid

uridine

hydroxyproline

pyrrole-2-carboxylic acid

adenosine

6-DHET

9-DiHETrE

10-DHOME

bovinic acid

and hydroxypyruvic acid. Nine metabolic pathways were involved

mainly with lipid metabolism and tricarboxylic acid cycle abnormality. There were 4 identical characteristic metabolite differences(guanidoacetic acid

deoxyuridine

cytidine

porphobilinogen) between group PXSRP and group SRYJP.

Conclusion

These results reveal the metabolomic mechanism of the formation of the clinical phenomes of PXSR and SRYJ associated with CRC and provide objective metabolomic evidence for the precise diagnosis of CRC clinical phenomes.

关键词

Keywords

references

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