Alteration of plasma metabolites associated with chemoradiosensitivity in esophageal squamous cell carcinoma via untargeted metabolomics approach

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Abstract

Background

To investigate the differences in plasma metabolomic characteristics between pathological complete response (pCR) and non-pCR patients and identify biomarker candidates for predicting the response to neoadjuvant chemoradiotherapy (nCRT) in esophageal squamous cell carcinoma (ESCC).

Methods

A total of 46 ESCC patients were included in this study. Gas chromatography time-of- flight mass spectrometry (GC-TOF/MS) technology was applied to detect the plasma samples collected before nCRT via untargeted metabolomics analysis.

Results

Five differentially expressed metabolites (out of 109) was found in plasma between pCR and non-pCR groups. Compared with non-pCR group, isocitric acid ( p = 0.0129), linoleic acid ( p = 0.0137), citric acid ( p = 0.0473) were upregulated, while L-histidine ( p = 0.0155), 3′4 dihydroxyhydrocinnamic acid ( p = 0.0339) were downregulated in the pCR plasma samples. Pathway analyses unveiled that citrate cycle (TCA cycle), glyoxylate and dicarboxylate metabolic pathway were associated with ESCC chemoradiosensitivity.

Conclusion

The present study provided supporting evidence that GC-TOF/MS based metabolomics approach allowed identification of metabolite differences between pCR and non-pCR patients in plasma levels, and the systemic metabolic status of patients may reflect the response of ESCC patient to neoadjuvant chemoradiotherapy.

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Most cited references 31

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Targeting glucose metabolism to suppress cancer progression: prospective of anti-glycolytic cancer therapy

Ali Abdel-Wahab, Waheed A Mahmoud, Randa M. Al-Harizy (2019)

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A distinct metabolic signature of human colorectal cancer with prognostic potential.

Yunping Qiu, Guoxiang Cai, Bingsen Zhou … (2014)

Metabolic phenotyping has provided important biomarker findings, which, unfortunately, are rarely replicated across different sample sets due to the variations from different analytical and clinical protocols used in the studies. To date, very few metabolic hallmarks in a given cancer type have been confirmed and validated by use of a metabolomic approach and other clinical modalities. Here, we report a metabolomics study to identify potential metabolite biomarkers of colorectal cancer with potential theranostic value. Gas chromatography-time-of-flight mass spectrometry (GC-TOFMS)-based metabolomics was used to analyze 376 surgical specimens, which were collected from four independent cohorts of patients with colorectal cancer at three hospitals located in China and City of Hope Comprehensive Cancer Center in the United States. Differential metabolites were identified and evaluated as potential prognostic markers. A targeted transcriptomic analysis of 29 colorectal cancer and 27 adjacent nontumor tissues was applied to analyze the gene expression levels for key enzymes associated with these shared metabolites. A panel of 15 significantly altered metabolites was identified, which demonstrates the ability to predict the rate of recurrence and survival for patients after surgery and chemotherapy. The targeted transcriptomic analysis suggests that the differential expression of these metabolites is due to robust metabolic adaptations in cancer cells to increased oxidative stress as well as demand for energy, and macromolecular substrates for cell growth and proliferation. These patients with colorectal cancer, despite their varied genetic background, mutations, pathologic stages, and geographic locations, shared a metabolic signature that is of great prognostic and therapeutic potential. ©2014 AACR.

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Searching for urine biomarkers of bladder cancer recurrence using a liquid chromatography-mass spectrometry and capillary electrophoresis-mass spectrometry metabolomics approach.

Ferran Algaba, Juliana Alberice, Coral Barbas … (2013)

The incidence and rate of recurrence of bladder cancer is high, particularly in developed countries, however current methods for diagnosis are limited to detecting high-grade tumours using often invasive methods. A panel of biomarkers to characterise tumours of different grades that could also distinguish between patients exhibiting the disease with first incidence or recurrence could be useful for bladder cancer diagnostics. In this study, potential metabolic biomarkers have been discovered through mass spectrometry based metabolomics of urine. Pre-treatment urine samples were collected from 48 patients diagnosed of urothelial bladder cancer. Patients were followed-up through the hospital pathological charts to identify whether and when the disease recurred or progressed. Subsequently, they were classified according to whether or not they suffered a tumour recurrence (recurrent or stable) as well as their risk group according to tumour grade and stage. Identified metabolites have been analysed in terms of disease characteristics (tumour stage and recurrence) and have provided an insight into bladder cancer progression. Using both liquid chromatography and capillary electrophoresis-mass spectrometry, a total of 27 metabolite features were highlighted as significantly different between patient groups. Some, for example histidine, phenylalanine, tyrosine and tryptophan have been previously linked with bladder cancer, however until now their connection with bladder cancer progression has not been previously reported. The candidate biomarkers revealed in this study could be useful in the clinic for diagnosis of bladder cancer and, through characterising the stage of the disease, could also be useful in prognostics. Copyright © 2013 Elsevier B.V. All rights reserved.

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Author and article information

Contributors

Jiahuan Zhou: zhoujh@biotecan.com

Fuyou Zhou: ayzhoufuyou@163.com

Journal

Journal ID (nlm-ta): BMC Cancer

Journal ID (iso-abbrev): BMC Cancer

Title: BMC Cancer

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2407

Publication date (Electronic): 2 September 2020

Publication date PMC-release: 2 September 2020

Publication date Collection: 2020

Volume: 20

Electronic Location Identifier: 835

Affiliations

[1 ]GRID grid.440151.5, Anyang Cancer Hospital, , The 4th Affiliated Hospital of Henan University of Science and Technology, ; No.1 Huanbin North Road, Anyang, 455000 Henan Province China

[2 ]Shanghai Zhangjiang Institue of Medical Innovation, Shanghai Biotecan Pharmaceuticals Co., Ltd., 180 Zhangheng Road, Shanghai, 201204 China

Article

Publisher ID: 7336

DOI: 10.1186/s12885-020-07336-9

PMC ID: 7466788

PubMed ID: 32878621

SO-VID: e9bf66d5-bef4-492c-8d45-aff86997038e

License:

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 : 13 April 2020

Date accepted : 24 August 2020

Funding

Funded by: National Nature Science Foundation of China

Award ID: U1504814

Award Recipient : Fuyou Zhou

Funded by: Major projects of Science and Technology Department in Henan Province

Award ID: 16110311200

Award ID: 161100311300

Award Recipient : Fuyou Zhou

Funded by: Anyang Science Foundation of Henan Province

Award ID: 2016

Award Recipient : Fuyou Zhou

Custom metadata

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: chemoradiosensitivity,esophageal squamous cell carcinoma,metabolomics,neoadjuvant therapy,untargeted metabolomics analysis

Data availability:

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: chemoradiosensitivity, esophageal squamous cell carcinoma, metabolomics, neoadjuvant therapy, untargeted metabolomics analysis

Alteration of plasma metabolites associated with chemoradiosensitivity in esophageal squamous cell carcinoma via untargeted metabolomics approach

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Abstract

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Conclusion

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Karger: Oncology

Most cited references 31

Targeting glucose metabolism to suppress cancer progression: prospective of anti-glycolytic cancer therapy

A distinct metabolic signature of human colorectal cancer with prognostic potential.

Searching for urine biomarkers of bladder cancer recurrence using a liquid chromatography-mass spectrometry and capillary electrophoresis-mass spectrometry metabolomics approach.

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