Untargeted metabolomics analysis of esophageal squamous cell cancer progression

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Abstract

90% of esophageal cancer are esophageal squamous cell carcinoma (ESCC) and ESCC has a very poor prognosis and high mortality. Nevertheless, the key metabolic pathways associated with ESCC progression haven’t been revealed yet. Metabolomics has become a new platform for biomarker discovery over recent years. We aim to elucidate dominantly metabolic pathway in all ESCC tumor/node/metastasis (TNM) stages and adjacent cancerous tissues. We collected 60 postoperative esophageal tissues and 15 normal tissues adjacent to the tumor, then performed Liquid Chromatography with tandem mass spectrometry (LC–MS/MS) analyses. The metabolites data was analyzed with metabolites differential and correlational expression heatmap according to stage I vs. con., stage I vs. stage II, stage II vs. stage III, and stage III vs. stage IV respectively. Metabolic pathways were acquired by Kyoto Encyclopedia of Genes and Genomes. (KEGG) pathway database. The metabolic pathway related genes were obtained via Gene Set Enrichment Analysis (GSEA). mRNA expression of ESCC metabolic pathway genes was detected by two public datasets: gene expression data series (GSE)23400 and The Cancer Genome Atlas (TCGA). Receiver operating characteristic curve (ROC) analysis is applied to metabolic pathway genes. 712 metabolites were identified in total. Glycerophospholipid metabolism was significantly distinct in ESCC progression. 16 genes of 77 genes of glycerophospholipid metabolism mRNA expression has differential significance between ESCC and normal controls. Phosphatidylserine synthase 1 (PTDSS1) and Lysophosphatidylcholine Acyltransferase1 (LPCAT1) had a good diagnostic value with Area under the ROC Curve (AUC) > 0.9 using ROC analysis. In this study, we identified glycerophospholipid metabolism was associated with the ESCC tumorigenesis and progression. Glycerophospholipid metabolism could be a potential therapeutic target of ESCC progression.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12967-022-03311-z.

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Author and article information

Contributors

Tao Yang:

ORCID: http://orcid.org/0000-0003-1273-0089

xiangfei654@hotmail.com

Qingchen Wu: qcwucq@163.com

Journal

Journal ID (nlm-ta): J Transl Med

Journal ID (iso-abbrev): J Transl Med

Title: Journal of Translational Medicine

Publisher: BioMed Central (London )

ISSN (Electronic): 1479-5876

Publication date (Electronic): 14 March 2022

Publication date PMC-release: 14 March 2022

Publication date Collection: 2022

Volume: 20

Electronic Location Identifier: 127

Affiliations

[1 ]GRID grid.452206.7, ISNI 0000 0004 1758 417X, Department of Thoracic and Cardiovascular Surgery, , The First Affiliated Hospital of Chongqing Medical University, ; Chongqing, 400016 China

[2 ]Department of Rehabilitation Medicine, Chengdu First Peoples’ Hospital, Chengdu, 610016 Sichuan China

[3 ]GRID grid.47100.32, ISNI 0000000419368710, Department of Pulmonary, Critical Care and Sleep Medicine, , School of Medicine of Yale University, ; New Haven, CT 06510 USA

Author information

Tao Yang http://orcid.org/0000-0003-1273-0089

Article

Publisher ID: 3311

DOI: 10.1186/s12967-022-03311-z

PMC ID: 8919643

PubMed ID: 35287685

SO-VID: 6f06e8fe-e47b-4dfc-9e3b-30a63a609d40

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Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 10 February 2022

Date accepted : 14 February 2022

Funding

Funded by: Chongqing Natural Science Foundation

Award ID: cstc2018jcyjAX0245

Award Recipient : Tao Yang

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ScienceOpen disciplines: Medicine

Keywords: esophageal squamous cell carcinoma,metabolomics,glycerophospholipid metabolism,ptdss1,lpcat1

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ScienceOpen disciplines: Medicine

Keywords: esophageal squamous cell carcinoma, metabolomics, glycerophospholipid metabolism, ptdss1, lpcat1

Untargeted metabolomics analysis of esophageal squamous cell cancer progression

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Supplementary Information

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Cancer Immunotherapy

Most cited references 50

NCBI GEO: archive for functional genomics data sets—update

A Cross-platform Toolkit for Mass Spectrometry and Proteomics

Metabolomics: beyond biomarkers and towards mechanisms.

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