Changing Metabolic Patterns along the Colorectal Adenoma–Carcinoma Sequence
Colorectal cancer (CRC) is a major public health burden and one of the leading causes of cancer-related deaths worldwide. Screening programs facilitate early diagnosis and can help to reduce poor outcomes. Serum metabolomics can extract vital molecular information that may increase the sensitivity a...
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MDPI AG
2022-01-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/11/3/721 |
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| author | Julia Tevini Sebastian K. Eder Ursula Huber-Schönauer David Niederseer Georg Strebinger Johanna M. Gostner Elmar Aigner Christian Datz Thomas K. Felder |
| author_facet | Julia Tevini Sebastian K. Eder Ursula Huber-Schönauer David Niederseer Georg Strebinger Johanna M. Gostner Elmar Aigner Christian Datz Thomas K. Felder |
| author_sort | Julia Tevini |
| collection | DOAJ |
| description | Colorectal cancer (CRC) is a major public health burden and one of the leading causes of cancer-related deaths worldwide. Screening programs facilitate early diagnosis and can help to reduce poor outcomes. Serum metabolomics can extract vital molecular information that may increase the sensitivity and specificity of colonoscopy in combination with histopathological examination. The present study identifies serum metabolite patterns of treatment-naïve patients, diagnosed with either advanced adenoma (AA) or CRC in colonoscopy screenings, in the framework of the SAKKOPI (Salzburg Colon Cancer Prevention Initiative) program. We used a targeted flow injection analysis and liquid chromatography-tandem mass spectrometry metabolomics approach (FIA- and LC-MS/MS) to characterise the serum metabolomes of an initial screening cohort and two validation cohorts (in total 66 CRC, 76 AA and 93 controls). The lipidome was significantly perturbed, with a proportion of lipid species being downregulated in CRC patients, as compared to AA and controls. The predominant alterations observed were in the levels of lyso-lipids, glycerophosphocholines and acylcarnitines, but additionally, variations in the quantity of hydroxylated sphingolipids could be detected. Changed amino acid metabolism was restricted mainly to metabolites of the arginine/dimethylarginine/NO synthase pathway. The identified metabolic divergences observed in CRC set the foundation for mechanistic studies to characterise biochemical pathways that become deregulated during progression through the adenoma to carcinoma sequence and highlight the key importance of lipid metabolites. Biomarkers related to these pathways could improve the sensitivity and specificity of diagnosis, as well as the monitoring of therapies. |
| first_indexed | 2024-03-09T23:41:18Z |
| format | Article |
| id | doaj.art-d8c14a46980f4b65b3092ffd07c30a3b |
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| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-09T23:41:18Z |
| publishDate | 2022-01-01 |
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| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-d8c14a46980f4b65b3092ffd07c30a3b2023-11-23T16:52:59ZengMDPI AGJournal of Clinical Medicine2077-03832022-01-0111372110.3390/jcm11030721Changing Metabolic Patterns along the Colorectal Adenoma–Carcinoma SequenceJulia Tevini0Sebastian K. Eder1Ursula Huber-Schönauer2David Niederseer3Georg Strebinger4Johanna M. Gostner5Elmar Aigner6Christian Datz7Thomas K. Felder8Department of Laboratory Medicine, Paracelsus Medical University, 5020 Salzburg, AustriaFirst Department of Medicine, Paracelsus Medical University, 5020 Salzburg, AustriaDepartment of Internal Medicine, Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University Salzburg, 5110 Oberndorf, AustriaDepartment of Cardiology, University Heart Center Zurich, University Hospital Zurich, University of Zurich, 8091 Zurich, SwitzerlandDepartment of Internal Medicine, Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University Salzburg, 5110 Oberndorf, AustriaInstitute of Medical Biochemistry, Innsbruck Medical University, 6020 Innsbruck, AustriaFirst Department of Medicine, Paracelsus Medical University, 5020 Salzburg, AustriaDepartment of Internal Medicine, Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University Salzburg, 5110 Oberndorf, AustriaDepartment of Laboratory Medicine, Paracelsus Medical University, 5020 Salzburg, AustriaColorectal cancer (CRC) is a major public health burden and one of the leading causes of cancer-related deaths worldwide. Screening programs facilitate early diagnosis and can help to reduce poor outcomes. Serum metabolomics can extract vital molecular information that may increase the sensitivity and specificity of colonoscopy in combination with histopathological examination. The present study identifies serum metabolite patterns of treatment-naïve patients, diagnosed with either advanced adenoma (AA) or CRC in colonoscopy screenings, in the framework of the SAKKOPI (Salzburg Colon Cancer Prevention Initiative) program. We used a targeted flow injection analysis and liquid chromatography-tandem mass spectrometry metabolomics approach (FIA- and LC-MS/MS) to characterise the serum metabolomes of an initial screening cohort and two validation cohorts (in total 66 CRC, 76 AA and 93 controls). The lipidome was significantly perturbed, with a proportion of lipid species being downregulated in CRC patients, as compared to AA and controls. The predominant alterations observed were in the levels of lyso-lipids, glycerophosphocholines and acylcarnitines, but additionally, variations in the quantity of hydroxylated sphingolipids could be detected. Changed amino acid metabolism was restricted mainly to metabolites of the arginine/dimethylarginine/NO synthase pathway. The identified metabolic divergences observed in CRC set the foundation for mechanistic studies to characterise biochemical pathways that become deregulated during progression through the adenoma to carcinoma sequence and highlight the key importance of lipid metabolites. Biomarkers related to these pathways could improve the sensitivity and specificity of diagnosis, as well as the monitoring of therapies.https://www.mdpi.com/2077-0383/11/3/721colorectal canceradenomametabolomicslipid metabolism |
| spellingShingle | Julia Tevini Sebastian K. Eder Ursula Huber-Schönauer David Niederseer Georg Strebinger Johanna M. Gostner Elmar Aigner Christian Datz Thomas K. Felder Changing Metabolic Patterns along the Colorectal Adenoma–Carcinoma Sequence Journal of Clinical Medicine colorectal cancer adenoma metabolomics lipid metabolism |
| title | Changing Metabolic Patterns along the Colorectal Adenoma–Carcinoma Sequence |
| title_full | Changing Metabolic Patterns along the Colorectal Adenoma–Carcinoma Sequence |
| title_fullStr | Changing Metabolic Patterns along the Colorectal Adenoma–Carcinoma Sequence |
| title_full_unstemmed | Changing Metabolic Patterns along the Colorectal Adenoma–Carcinoma Sequence |
| title_short | Changing Metabolic Patterns along the Colorectal Adenoma–Carcinoma Sequence |
| title_sort | changing metabolic patterns along the colorectal adenoma carcinoma sequence |
| topic | colorectal cancer adenoma metabolomics lipid metabolism |
| url | https://www.mdpi.com/2077-0383/11/3/721 |
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