NMR-Metabolomics Reveals a Metabolic Shift after Surgical Resection of Non-Small Cell Lung Cancer
Background: Lung cancer can be detected by measuring the patient’s plasma metabolomic profile using nuclear magnetic resonance (NMR) spectroscopy. This NMR-based plasma metabolomic profile is patient-specific and represents a snapshot of the patient’s metabolite concentrations. The onset of non-smal...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/7/2127 |
| _version_ | 1797608295135969280 |
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| author | Elien Derveaux Melvin Geubbelmans Maarten Criel Ingel Demedts Ulrike Himpe Kurt Tournoy Piet Vercauter Erik Johansson Dirk Valkenborg Karolien Vanhove Liesbet Mesotten Peter Adriaensens Michiel Thomeer |
| author_facet | Elien Derveaux Melvin Geubbelmans Maarten Criel Ingel Demedts Ulrike Himpe Kurt Tournoy Piet Vercauter Erik Johansson Dirk Valkenborg Karolien Vanhove Liesbet Mesotten Peter Adriaensens Michiel Thomeer |
| author_sort | Elien Derveaux |
| collection | DOAJ |
| description | Background: Lung cancer can be detected by measuring the patient’s plasma metabolomic profile using nuclear magnetic resonance (NMR) spectroscopy. This NMR-based plasma metabolomic profile is patient-specific and represents a snapshot of the patient’s metabolite concentrations. The onset of non-small cell lung cancer (NSCLC) causes a change in the metabolite profile. However, the level of metabolic changes after complete NSCLC removal is currently unknown. Patients and methods: Fasted pre- and postoperative plasma samples of 74 patients diagnosed with resectable stage I-IIIA NSCLC were analyzed using <sup>1</sup>H-NMR spectroscopy. NMR spectra (<i>s</i> = 222) representing two preoperative and one postoperative plasma metabolite profile at three months after surgical resection were obtained for all patients. In total, 228 predictors, i.e., 228 variables representing plasma metabolite concentrations, were extracted from each NMR spectrum. Two types of supervised multivariate discriminant analyses were used to train classifiers presenting a strong differentiation between the pre- and postoperative plasma metabolite profiles. The validation of these trained classification models was obtained by using an independent dataset. Results: A trained multivariate discriminant classification model shows a strong differentiation between the pre- and postoperative NSCLC profiles with a specificity of 96% (95% CI [86–100]) and a sensitivity of 92% (95% CI [81–98]). Validation of this model results in an excellent predictive accuracy of 90% (95% CI [77–97]) and an AUC value of 0.97 (95% CI [0.93–1]). The validation of a second trained model using an additional preoperative control sample dataset confirms the separation of the pre- and postoperative profiles with a predictive accuracy of 93% (95% CI [82–99]) and an AUC value of 0.97 (95% CI [0.93–1]). Metabolite analysis reveals significantly increased lactate, cysteine, asparagine and decreased acetate levels in the postoperative plasma metabolite profile. Conclusions: The results of this paper demonstrate that surgical removal of NSCLC generates a detectable metabolic shift in blood plasma. The observed metabolic shift indicates that the NSCLC metabolite profile is determined by the tumor’s presence rather than donor-specific features. Furthermore, the ability to detect the metabolic difference before and after surgical tumor resection strongly supports the prospect that NMR-generated metabolite profiles via blood samples advance towards early detection of NSCLC recurrence. |
| first_indexed | 2024-03-11T05:41:27Z |
| format | Article |
| id | doaj.art-fd70c8641f9344e384cd416bfe2bf893 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T05:41:27Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-fd70c8641f9344e384cd416bfe2bf8932023-11-17T16:26:33ZengMDPI AGCancers2072-66942023-04-01157212710.3390/cancers15072127NMR-Metabolomics Reveals a Metabolic Shift after Surgical Resection of Non-Small Cell Lung CancerElien Derveaux0Melvin Geubbelmans1Maarten Criel2Ingel Demedts3Ulrike Himpe4Kurt Tournoy5Piet Vercauter6Erik Johansson7Dirk Valkenborg8Karolien Vanhove9Liesbet Mesotten10Peter Adriaensens11Michiel Thomeer12Faculty of Medicine and Life Sciences, Hasselt University, Martelarenlaan 42, B-3500 Hasselt, BelgiumData Science Institute, Hasselt University, Agoralaan 1, B-3590 Diepenbeek, BelgiumDepartment of Respiratory Medicine, Ziekenhuis Oost-Limburg, Schiepse Bos 6, B-3600 Genk, BelgiumDepartment of Respiratory Medicine, AZ Delta, Deltalaan 1, B-8800 Roeselare, BelgiumDepartment of Respiratory Medicine, AZ Delta, Deltalaan 1, B-8800 Roeselare, BelgiumDepartment of Respiratory Medicine, Onze-Lieve-Vrouw Ziekenhuis, Moorselbaan 164, B-9300 Aalst, BelgiumDepartment of Respiratory Medicine, Onze-Lieve-Vrouw Ziekenhuis, Moorselbaan 164, B-9300 Aalst, BelgiumSartorius Stedim Data Analytics AB, Östra Strandgatan 24, 903 33 Umeå, SwedenData Science Institute, Hasselt University, Agoralaan 1, B-3590 Diepenbeek, BelgiumApplied and Analytical Chemistry, Institute for Materials Research, Hasselt University, Agoralaan 1—Building D, B-3590 Diepenbeek, BelgiumFaculty of Medicine and Life Sciences, Hasselt University, Martelarenlaan 42, B-3500 Hasselt, BelgiumApplied and Analytical Chemistry, Institute for Materials Research, Hasselt University, Agoralaan 1—Building D, B-3590 Diepenbeek, BelgiumFaculty of Medicine and Life Sciences, Hasselt University, Martelarenlaan 42, B-3500 Hasselt, BelgiumBackground: Lung cancer can be detected by measuring the patient’s plasma metabolomic profile using nuclear magnetic resonance (NMR) spectroscopy. This NMR-based plasma metabolomic profile is patient-specific and represents a snapshot of the patient’s metabolite concentrations. The onset of non-small cell lung cancer (NSCLC) causes a change in the metabolite profile. However, the level of metabolic changes after complete NSCLC removal is currently unknown. Patients and methods: Fasted pre- and postoperative plasma samples of 74 patients diagnosed with resectable stage I-IIIA NSCLC were analyzed using <sup>1</sup>H-NMR spectroscopy. NMR spectra (<i>s</i> = 222) representing two preoperative and one postoperative plasma metabolite profile at three months after surgical resection were obtained for all patients. In total, 228 predictors, i.e., 228 variables representing plasma metabolite concentrations, were extracted from each NMR spectrum. Two types of supervised multivariate discriminant analyses were used to train classifiers presenting a strong differentiation between the pre- and postoperative plasma metabolite profiles. The validation of these trained classification models was obtained by using an independent dataset. Results: A trained multivariate discriminant classification model shows a strong differentiation between the pre- and postoperative NSCLC profiles with a specificity of 96% (95% CI [86–100]) and a sensitivity of 92% (95% CI [81–98]). Validation of this model results in an excellent predictive accuracy of 90% (95% CI [77–97]) and an AUC value of 0.97 (95% CI [0.93–1]). The validation of a second trained model using an additional preoperative control sample dataset confirms the separation of the pre- and postoperative profiles with a predictive accuracy of 93% (95% CI [82–99]) and an AUC value of 0.97 (95% CI [0.93–1]). Metabolite analysis reveals significantly increased lactate, cysteine, asparagine and decreased acetate levels in the postoperative plasma metabolite profile. Conclusions: The results of this paper demonstrate that surgical removal of NSCLC generates a detectable metabolic shift in blood plasma. The observed metabolic shift indicates that the NSCLC metabolite profile is determined by the tumor’s presence rather than donor-specific features. Furthermore, the ability to detect the metabolic difference before and after surgical tumor resection strongly supports the prospect that NMR-generated metabolite profiles via blood samples advance towards early detection of NSCLC recurrence.https://www.mdpi.com/2072-6694/15/7/2127non-small cell lung cancerNMR spectroscopymetabolomics |
| spellingShingle | Elien Derveaux Melvin Geubbelmans Maarten Criel Ingel Demedts Ulrike Himpe Kurt Tournoy Piet Vercauter Erik Johansson Dirk Valkenborg Karolien Vanhove Liesbet Mesotten Peter Adriaensens Michiel Thomeer NMR-Metabolomics Reveals a Metabolic Shift after Surgical Resection of Non-Small Cell Lung Cancer Cancers non-small cell lung cancer NMR spectroscopy metabolomics |
| title | NMR-Metabolomics Reveals a Metabolic Shift after Surgical Resection of Non-Small Cell Lung Cancer |
| title_full | NMR-Metabolomics Reveals a Metabolic Shift after Surgical Resection of Non-Small Cell Lung Cancer |
| title_fullStr | NMR-Metabolomics Reveals a Metabolic Shift after Surgical Resection of Non-Small Cell Lung Cancer |
| title_full_unstemmed | NMR-Metabolomics Reveals a Metabolic Shift after Surgical Resection of Non-Small Cell Lung Cancer |
| title_short | NMR-Metabolomics Reveals a Metabolic Shift after Surgical Resection of Non-Small Cell Lung Cancer |
| title_sort | nmr metabolomics reveals a metabolic shift after surgical resection of non small cell lung cancer |
| topic | non-small cell lung cancer NMR spectroscopy metabolomics |
| url | https://www.mdpi.com/2072-6694/15/7/2127 |
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