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Cancers
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Cancer Metabolomic Analysis
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Cancer Metabolomic Analysis

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Tumor Microenvironment".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 12115

Special Issue Editors

Prof. Dr. Masahiro Sugimoto

E-Mail Website
Guest Editor
Research and Development Center for Minimally Invasive Therapies, Institute of Medical Science, Tokyo Medical University, Tokyo 108-8639, Japan
Interests: metabolomics; bioinformatics; systems biology; artificial intelligence; cancer
Dr. Sho Tabata

E-Mail Website
Guest Editor
Institute for Protein Research, Osaka University, Osaka 565-0871, Japan
Interests: cancer; metabolism; metabolomics; epithelial-mesenchymal transition
Dr. Yoshihisa Hirota

E-Mail Website
Guest Editor
Department of Bioscience and Engineering, College of Systems Engineering and Science, Shibaura Institute of Technology, Saitama 337-8570, Japan
Interests: fat-soluble vitamin; molecular nutrition; pharmaceutic therapy; cancer; metabolism

Special Issue Information

Dear Colleagues,

Cancer cells shift metabolic pathways to satisfy the demands of their rapid growth and proliferation. Various properties of cancer, such as genetic and immune abnormalities, cause these metabolic alterations. In addition, physical conditions, e.g. the tumour microenvironment, also contribute to yielding the cell heterogeneities. Metabolomics is one of the approaches to capture the holistic view of the metabolic pathways. High sensitive and high-throughput technologies, such as mass spectrometry and nuclear magnetic resonance, enable us to identify and quantify hundreds of metabolites. This high-dimensional data with sophisticated data analyses realize data-driven science to understand the holistic view and find new insight into cancer metabolism. This Special Issue highlights metabolomics to understand the cancer cell metabolites. The applications toward developing a diagnosis, treatments, and relevant technologies are also highlighted.

Prof. Dr. Masahiro Sugimoto
Dr. Sho Tabata
Dr. Yoshihisa Hirota
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cancer
  • metabolism
  • metabolomics
  • mass spectrometry
  • nuclear magnetic resonance
  • cancer drug discovery
  • cancer nutrition

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Published Papers (5 papers)

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Research

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13 pages, 2156 KiB  
Article
Analysis of the Circulating Metabolome of Patients with Cutaneous, Mucosal and Uveal Melanoma Reveals Distinct Metabolic Profiles with Implications for Response to Immunotherapy
by Maysa Vilbert, Erica C. Koch, April A. N. Rose, Rob C. Laister, Diana Gray, Valentin Sotov, Susanne Penny, Anna Spreafico, Devanand M. Pinto, Marcus O. Butler and Samuel D. Saibil
Cancers 2023, 15(14), 3708; https://doi.org/10.3390/cancers15143708 - 21 Jul 2023
Cited by 1 | Viewed by 1638
Abstract
Cutaneous melanoma (CM) patients respond better to immune checkpoint inhibitors (ICI) than mucosal and uveal melanoma patients (MM/UM). Aiming to explore these differences and understand the distinct response to ICI, we evaluated the serum metabolome of advanced CM, MM, and UM patients. Levels [...] Read more.
Cutaneous melanoma (CM) patients respond better to immune checkpoint inhibitors (ICI) than mucosal and uveal melanoma patients (MM/UM). Aiming to explore these differences and understand the distinct response to ICI, we evaluated the serum metabolome of advanced CM, MM, and UM patients. Levels of 115 metabolites were analyzed in samples collected before ICI, using a targeted metabolomics platform. In our analysis, molecules involved in the tryptophan-kynurenine axis distinguished UM/MM from CM. UM/MM patients had higher levels of 3-hydroxykynurenine (3-HKyn), whilst patients with CM were found to have higher levels of kynurenic acid (KA). The KA/3-HKyn ratio was significantly higher in CM versus the other subtypes. UM, the most ICI-resistant subtype, was also associated with higher levels of sphingomyelin-d18:1/22:1 and the polyamine spermine (SPM). Overall survival was prolonged in a cohort of CM patients with lower SPM levels, suggesting there are also conserved metabolic factors promoting ICI resistance across melanoma subtypes. Our study revealed a distinct metabolomic profile between the most resistant melanoma subtypes, UM and MM, compared to CM. Alterations within the kynurenine pathway, polyamine metabolism, and sphingolipid metabolic pathway may contribute to the poor response to ICI. Understanding the different metabolomic profiles introduces opportunities for novel therapies with potential synergic activity to ICI, to improve responses of UM/MM. Full article
(This article belongs to the Special Issue Cancer Metabolomic Analysis)
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27 pages, 4943 KiB  
Article
The Relationship between Histological Composition and Metabolic Profile in Breast Tumors and Peritumoral Tissue Determined with 1H HR-MAS NMR Spectroscopy
by Agnieszka Skorupa, Mateusz Ciszek, Maria Turska-d’Amico, Ewa Stobiecka, Ewa Chmielik, Ryszard Szumniak, Andrea d’Amico, Łukasz Boguszewicz and Maria Sokół
Cancers 2023, 15(4), 1283; https://doi.org/10.3390/cancers15041283 - 17 Feb 2023
Cited by 2 | Viewed by 2154
Abstract
Breast tumors constitute the complex entities composed of cancer cells and stromal components. The compositional heterogeneity should be taken into account in bulk tissue metabolomics studies. The aim of this work was to find the relation between the histological content and 1H [...] Read more.
Breast tumors constitute the complex entities composed of cancer cells and stromal components. The compositional heterogeneity should be taken into account in bulk tissue metabolomics studies. The aim of this work was to find the relation between the histological content and 1H HR-MAS (high-resolution magic angle spinning nuclear magnetic resonance) metabolic profiles of the tissue samples excised from the breast tumors and the peritumoral areas in 39 patients diagnosed with invasive breast carcinoma. The total number of the histologically verified specimens was 140. The classification accuracy of the OPLS-DA (Orthogonal Partial Least Squares Discriminant Analysis) model differentiating the cancerous from non-involved samples was 87% (sensitivity of 72.2%, specificity of 92.3%). The metabolic contents of the epithelial and stromal compartments were determined from a linear regression analysis of the levels of the evaluated compounds against the cancer cell fraction in 39 samples composed mainly of cancer cells and intratumoral fibrosis. The correlation coefficients between the levels of several metabolites and a tumor purity were found to be dependent on the tumor grade (I vs II/III). The comparison of the levels of the metabolites in the intratumoral fibrosis (obtained from the extrapolation of the regression lines to 0% cancer content) to those levels in the fibrous connective tissue beyond the tumors revealed a profound metabolic reprogramming in the former tissue. The joint analysis of the metabolic profiles of the stromal and epithelial compartments in the breast tumors contributes to the increased understanding of breast cancer biology. Full article
(This article belongs to the Special Issue Cancer Metabolomic Analysis)
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12 pages, 2600 KiB  
Article
The Riddle of Cetuximab-Related Skin Toxicity: 1H-NMR Sebum Analysis Revealed Dynamic Lipid Alterations Associated with Skin Toxicity Development in Metastatic Colorectal Cancer Patients
by Asia Saorin, Emanuela Di Gregorio, Angela Buonadonna, Gianmaria Miolo and Giuseppe Corona
Cancers 2022, 14(21), 5308; https://doi.org/10.3390/cancers14215308 - 28 Oct 2022
Cited by 2 | Viewed by 1629
Abstract
The epidermal growth factor receptor inhibitor (EGFRIs) treatments are commonly associated with the development of adverse skin effects. This study aims to investigate the lipid composition change in sebum during cetuximab-based treatment in an attempt to identify specific metabolic signatures useful in predicting [...] Read more.
The epidermal growth factor receptor inhibitor (EGFRIs) treatments are commonly associated with the development of adverse skin effects. This study aims to investigate the lipid composition change in sebum during cetuximab-based treatment in an attempt to identify specific metabolic signatures useful in predicting the occurrence of severe skin toxicity. Sebum from 30 metastatic colorectal cancer (mCRC) patients was collected at three time points during the targeted therapy by the application of Sebutape® on the forehead, and the major lipid classes were analyzed and quantified by 1H-NMR. Univariate analysis was performed to reveal significant alterations among patients in sebum production as well as lipid composition and over the course of cetuximab therapy. A transient but significant decrease in sebum production associated with a reduction in the relative content of triglycerides (TG) and squalene (SQ) was found to be induced by cetuximab administration. The reduction of these two lipid classes was also found to be associated with the severity of skin rash experienced by patients. The results of this study indicate that cetuximab-based treatment can reduce sebum gland activity, leading to an overall decrease in sebum production and the induction of specific modifications to its composition. The extent of the loss of skin barrier function may be important for determining the severity of skin toxicity development. Full article
(This article belongs to the Special Issue Cancer Metabolomic Analysis)
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20 pages, 1966 KiB  
Article
Ex Vivo High-Resolution Magic Angle Spinning (HRMAS) 1H NMR Spectroscopy for Early Prostate Cancer Detection
by Annabel Steiner, Stefan Andreas Schmidt, Cara Sophie Fellmann, Johannes Nowak, Chin-Lee Wu, Adam Scott Feldman, Meinrad Beer and Leo L. Cheng
Cancers 2022, 14(9), 2162; https://doi.org/10.3390/cancers14092162 - 26 Apr 2022
Cited by 4 | Viewed by 2268
Abstract
The aim of our study was to assess ex vivo HRMAS (high-resolution magic angle spinning) 1H NMR spectroscopy as a diagnostic tool for early PCa detection by testing whether metabolomic alterations in prostate biopsy samples can predict future PCa diagnosis. In a [...] Read more.
The aim of our study was to assess ex vivo HRMAS (high-resolution magic angle spinning) 1H NMR spectroscopy as a diagnostic tool for early PCa detection by testing whether metabolomic alterations in prostate biopsy samples can predict future PCa diagnosis. In a primary prospective study (04/2006–10/2018), fresh biopsy samples of 351 prostate biopsy patients were NMR spectroscopically analyzed (Bruker 14.1 Tesla, Billerica, MA, USA) and histopathologically evaluated. Three groups of 16 patients were compared: group 1 and 2 represented patients whose NMR scanned biopsy was histobenign, but patients in group 1 were diagnosed with cancer before the end of the study period, whereas patients in group 2 remained histobenign. Group 3 included cancer patients. Single-metabolite concentrations and metabolomic profiles were not only able to separate histobenign and malignant prostate tissue but also to differentiate between samples of histobenign patients who received a PCa diagnosis in the following years and those who remained histobenign. Our results support the hypothesis that metabolomic alterations significantly precede histologically visible changes, making metabolomic information highly beneficial for early PCa detection. Thanks to its predictive power, metabolomic information can be very valuable for the individualization of PCa active surveillance strategies. Full article
(This article belongs to the Special Issue Cancer Metabolomic Analysis)
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Review

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29 pages, 1599 KiB  
Review
The Ubiquitin–Proteasome System in Tumor Metabolism
by Jie Wang, Yuandi Xiang, Mengqi Fan, Shizhen Fang and Qingquan Hua
Cancers 2023, 15(8), 2385; https://doi.org/10.3390/cancers15082385 - 20 Apr 2023
Cited by 7 | Viewed by 3487
Abstract
Metabolic reprogramming, which is considered a hallmark of cancer, can maintain the homeostasis of the tumor environment and promote the proliferation, survival, and metastasis of cancer cells. For instance, increased glucose uptake and high glucose consumption, known as the “Warburg effect,” play an [...] Read more.
Metabolic reprogramming, which is considered a hallmark of cancer, can maintain the homeostasis of the tumor environment and promote the proliferation, survival, and metastasis of cancer cells. For instance, increased glucose uptake and high glucose consumption, known as the “Warburg effect,” play an essential part in tumor metabolic reprogramming. In addition, fatty acids are harnessed to satisfy the increased requirement for the phospholipid components of biological membranes and energy. Moreover, the anabolism/catabolism of amino acids, such as glutamine, cystine, and serine, provides nitrogen donors for biosynthesis processes, development of the tumor inflammatory environment, and signal transduction. The ubiquitin–proteasome system (UPS) has been widely reported to be involved in various cellular biological activities. A potential role of UPS in the metabolic regulation of tumor cells has also been reported, but the specific regulatory mechanism has not been elucidated. Here, we review the role of ubiquitination and deubiquitination modification on major metabolic enzymes and important signaling pathways in tumor metabolism to inspire new strategies for the clinical treatment of cancer. Full article
(This article belongs to the Special Issue Cancer Metabolomic Analysis)
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