血液代谢标志物在原发性肝癌治疗反应及预后预测中的应用

刘志英; 周智航; 何松

doi:10.3969/j.issn.1001-5256.2023.10.028

血液代谢标志物在原发性肝癌治疗反应及预后预测中的应用

DOI: 10.3969/j.issn.1001-5256.2023.10.028

刘志英^{1, 2},
周智航¹,
何松^1, , ,

1.
重庆医科大学附属第二医院消化内科，重庆 400010
2.
西安市中心医院消化内科，西安 710000

基金项目:

重庆市自然科学基金 (2022NSCQ－MSX1038);

重庆市自然科学基金 (2022NSCQ－MSX0775)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：刘志英对文章的思路及撰写有关键贡献；周智航和何松参与修改文章关键内容。

详细信息

通信作者:
何松， hedoctor65@cqmu.edu.cn （ORCID： 0000－0002－6424－4974）

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出版历程
- 收稿日期: 2022-12-27
- 录用日期: 2023-02-21
- 出版日期: 2023-10-30

Research advances in the role of blood metabolic markers in the treatment response and prognosis prediction of primary liver cancer

Zhiying LIU^{1, 2},
Zhihang ZHOU¹,
Song HE^{1
, ,
,}

1.
Department of Gastroenterology，The Second Affiliated Hospital of Chongqing Medical University，Chongqing 400010，China
2.
Department of Gastroenterology，Xi’an Central Hospital，Xi’an 710000，China

Research funding:

Natural Science Foundation of Chongqing (2022NSCQ－MSX1038);

Natural Science Foundation of Chongqing (2022NSCQ－MSX0775)

More Information

Corresponding author: HE Song， hedoctor65@cqmu.edu.cn （ORCID： 0000－0002－6424－4974）

摘要

摘要: 原发性肝癌是全球严重的癌症负担之一。代谢重编程是癌症的一种表型，血液代谢标志物与代谢重编程密切相关，可以预测肝癌患者复发风险和生存期情况或评估肝癌治疗反应，对于分层管理患者、制订合理治疗策略以及改善患者预后具有重要意义。本文回顾了近年来关于肝癌治疗反应评估和预后预测的血液代谢组学研究，归纳了具有预测意义的血液代谢物并简述其作用机制，分析了该领域的研究现状、存在问题和发展前景。认为芳香族氨基酸、脂质、胆汁酸等代谢物对肝癌预后预测有重要的临床应用价值，且代谢组学技术在寻找有用代谢物方面具有巨大潜力，但存在技术限制、研究不足、多重影响因素等许多有待解决的问题。
- 肝肿瘤 /
- 生物标记 /
- 治疗学 /
- 预后
Abstract: Primary liver cancer is one of the most severe cancer burdens around the world. Metabolic reprogramming is one phenotype of cancer， and blood metabolic markers are closely associated with metabolic reprogramming and can predict the risk of recurrence and survival or assess the treatment response of liver cancer， with important significance in the stratified management of patients， the development of rational treatment strategies， and the improvement of patient prognosis. By reviewing the recent studies on blood metabolomics in assessing the treatment response or predicting the prognosis of liver cancer， this article summarizes the blood metabolites with predictive significance and their mechanism of action and analyzes the current research status， existing problems， and prospects of this field. It is believed that the metabolites， such as aromatic amino acids， lipids， and bile acids， have an important clinical value in predicting the prognosis of liver cancer， and metabolomics technology has great potential in finding useful metabolites， but there are still many issues to be solved， such as technical limitations， insufficient studies， and multiple influencing factors.
- Liver Neoplasms /
- Biomarkers /
- Therapeutics /
- Prognosis

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表 1 预测肝癌治疗反应或预后的血液代谢物

Table 1. Blood metabolites for predicting treatment response or prognosis of liver cancer

治疗方式	参考文献	检测平台	代谢物	临床模型	OS	复发	主要病因
肝切除术	［17］	HPLC－MS	苯丙氨酸、胆碱	GPI评分和PMP评分	负相关		HBV
	［18］	pseudotargeted GC－MS	苯丙氨酸、半乳糖	RS_OS	负相关		HBV
	［18］	pseudotargeted GC－MS	半乳糖、酪氨酸	RS_DFS		负相关	HBV
	［19］	HPLC－MS	视黄醇、视黄醛		正相关		HBV
肝切除术/射频消融	［20］	UHPLC－QTOF－MS	1，25－二羟基胆固醇、肉豆蔻棕榈酸、12－酮基去氧胆酸、LysoPC（21∶4）和LysoPE（22∶2）		正相关		HCV
肝切除术/肝移植	［12］	HPLC－MS	DL－3－苯基乳酸、甘胆酸、L－色氨酸和1－甲基烟酰胺		负相关
肝移植	［21］	HPLC－MS	PC（16∶0/P－18∶1）、PC（18∶2/OH－16∶0）、胆酸	术前血浆列线图		正相关
射频消融、索拉非尼靶向治疗	［15］	NMR	肌醇、二甲胺		正相关		酒精
	［15］	NMR	总胆固醇、低密度脂蛋白胆固醇和低密度脂蛋白颗粒		负相关		酒精
	［16］	NMR	酪氨酸		正相关		HCV
放射治疗	［22］	GC－MS，LC－MS	脂肪酸、甘油磷脂和酰基肉碱等				酒精、HCV
放射治疗	［22］	GC－MS，LC－MS	丝氨酸、丙氨酸、牛磺酸和脂质代谢物				酒精、HCV
注：HPLC，超高效液相色谱；QTOF，四极杆飞行时间；PC，磷脂酰胆碱；LysoPE，溶血磷脂酰乙醇胺；RS，风险评分；SBRT，立体定向放射治疗；OS，总生存期；DFS，无病生存期；正/负相关，代谢物与OS/复发之间的相关性。

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