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通过质谱成像对肝细胞癌中重编程代谢进行空间分辨可视化

Spatially resolved visualization of reprogrammed metabolism in hepatocellular carcinoma by mass spectrometry imaging.

作者信息

Ma Bangzhen, Zhang Yang, Ma Jiwei, Chen Xinguo, Sun Chenglong, Qin Chengkun

机构信息

Shandong Provincial Hospital, Shandong University, Jinan, 250021, China.

Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, China.

出版信息

Cancer Cell Int. 2023 Aug 24;23(1):177. doi: 10.1186/s12935-023-03027-0.

DOI:10.1186/s12935-023-03027-0
PMID:37620880
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10464423/
Abstract

BACKGROUND

Metabolic reprogramming refers to tumor-associated metabolic alterations during tumorigenesis and has been regarded as one of the most important features of cancer. Profiling the altered metabolites and lipids in hepatocellular carcinoma with spatial signature will not only enhance our understanding of tumor metabolic reprogramming, but also offer potential metabolic liabilities that might be exploited for hepatocellular carcinoma therapy.

METHODS

We perform matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) analysis on both hepatocellular carcinoma xenograft mouse model and hepatocellular carcinoma patients. Discriminatory metabolites that altered during the development of hepatocellular carcinoma are screened and imaged in xenograft mouse model and are further validated in 21 hepatocellular carcinoma patients.

RESULTS

We discover stepwise metabolic alterations and progressively increasing metabolic heterogeneity during the growth of hepatocellular carcinoma. Arginine and its metabolites spermine and spermidine, choline and phosphatidylcholine metabolism, and fatty acids were found to be significantly reprogrammed in hepatocellular carcinoma tissues.

CONCLUSIONS

The spatially resolved profiling of the metabolites and lipids in highly heterogeneous hepatocellular carcinoma tissue will contribute to obtaining precise metabolic information for the understanding of tumor metabolic reprogramming.

摘要

背景

代谢重编程是指肿瘤发生过程中与肿瘤相关的代谢改变，被认为是癌症最重要的特征之一。对具有空间特征的肝细胞癌中改变的代谢物和脂质进行分析，不仅能增进我们对肿瘤代谢重编程的理解，还能提供可能用于肝细胞癌治疗的潜在代谢靶点。

方法

我们对肝细胞癌异种移植小鼠模型和肝细胞癌患者均进行了基质辅助激光解吸/电离质谱成像（MALDI-MSI）分析。在异种移植小鼠模型中筛选并成像在肝细胞癌发生发展过程中改变的鉴别性代谢物，并在21例肝细胞癌患者中进一步验证。

结果

我们发现肝细胞癌生长过程中存在逐步的代谢改变和逐渐增加的代谢异质性。精氨酸及其代谢物精胺和亚精胺、胆碱和磷脂酰胆碱代谢以及脂肪酸在肝细胞癌组织中被发现有显著的重编程。

结论

对高度异质性的肝细胞癌组织中的代谢物和脂质进行空间分辨分析，将有助于获得精确的代谢信息，以理解肿瘤代谢重编程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e0/10464423/e0e1c52a45cd/12935_2023_3027_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e0/10464423/c9fd9e742252/12935_2023_3027_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e0/10464423/eb1726ba4111/12935_2023_3027_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e0/10464423/f12709512674/12935_2023_3027_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e0/10464423/caf43deded9e/12935_2023_3027_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e0/10464423/5d7331f109d1/12935_2023_3027_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e0/10464423/e0e1c52a45cd/12935_2023_3027_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e0/10464423/c9fd9e742252/12935_2023_3027_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e0/10464423/eb1726ba4111/12935_2023_3027_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e0/10464423/f12709512674/12935_2023_3027_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e0/10464423/caf43deded9e/12935_2023_3027_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e0/10464423/5d7331f109d1/12935_2023_3027_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e0/10464423/e0e1c52a45cd/12935_2023_3027_Fig6_HTML.jpg

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