Specific changes in amino acid profiles in monocytes of patients with breast, lung, colorectal and ovarian cancers
IntroductionImmunometabolism is essential factor of tumor progression, and tumor-associated macrophages are characterized by substantial changes in their metabolic status. In this study for the first time, we applied targeted amino acid LC-MS/MS analysis to compare amino acid metabolism of circulati...
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1332043/full |
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| author | Vitaliy Chagovets Natalia Starodubtseva Natalia Starodubtseva Alisa Tokareva Anastasia Novoselova Marina Patysheva Marina Patysheva Irina Larionova Irina Larionova Irina Larionova Elizaveta Prostakishina Elizaveta Prostakishina Militsa Rakina Militsa Rakina Anna Kazakova Evgenii Topolnitskiy Nikolay Shefer Julia Kzhyshkowska Julia Kzhyshkowska Julia Kzhyshkowska Julia Kzhyshkowska Vladimir Frankevich Vladimir Frankevich Gennadiy Sukhikh |
| author_facet | Vitaliy Chagovets Natalia Starodubtseva Natalia Starodubtseva Alisa Tokareva Anastasia Novoselova Marina Patysheva Marina Patysheva Irina Larionova Irina Larionova Irina Larionova Elizaveta Prostakishina Elizaveta Prostakishina Militsa Rakina Militsa Rakina Anna Kazakova Evgenii Topolnitskiy Nikolay Shefer Julia Kzhyshkowska Julia Kzhyshkowska Julia Kzhyshkowska Julia Kzhyshkowska Vladimir Frankevich Vladimir Frankevich Gennadiy Sukhikh |
| author_sort | Vitaliy Chagovets |
| collection | DOAJ |
| description | IntroductionImmunometabolism is essential factor of tumor progression, and tumor-associated macrophages are characterized by substantial changes in their metabolic status. In this study for the first time, we applied targeted amino acid LC-MS/MS analysis to compare amino acid metabolism of circulating monocytes isolated from patients with breast, ovarian, lung, and colorectal cancer.MethodsMonocyte metabolomics was analyzed by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/ MS) analysis of amino acid extracts. The targeted analysis of 26 amino acids was conducted by LCMS/MS on an Agilent 6460 triple quadrupole mass spectrometer equipped with an electrospray ionization source and an Agilent 1260 II liquid chromatograph.ResultsComparison of monocytes of cancer patients with monocytes of healthy control individuals demonstrated that in breast cancer most pronounced changes were identified for tryptophan (AUC = 0.76); for ovarian cancer, aminobutyric acid was significantly elevated (AUC= 1.00); for lung cancer significant changes we indented for citrulline (AUC = 0.70). In order to identify key amino acids that are characteristic for monocytes in specific cancer types, we compared each individual cancer with other 3 types of cancer. We found, that aspartic acid and citrulline are specific for monocytes of patients with colorectal cancer (p<0.001, FC = 1.40 and p=0.003, FC = 1.42 respectively). Citrulline, sarcosine and glutamic acid are ovarian cancer-specific amino acids (p = 0.003, FC = 0.78, p = 0.003, FC = 0.62, p = 0.02, FC = 0.78 respectively). Glutamine, methionine and phenylalanine (p = 0.048, FC = 1.39. p = 0.03, FC = 1.27 and p = 0.02, FC = 1.41) are lung cancer-specific amino acids. Ornithine in monocytes demonstrated strong positive correlation (r = 0.63) with lymph node metastasis incidence in breast cancer patients. Methyl histidine and cysteine in monocytes had strong negative correlation with lymph node metastasis in ovarian cancer patients (r = -0.95 and r = -0.95 respectively). Arginine, citrulline and ornithine have strong negative correlation with tumor size (r = -0.78, citrulline) and lymph node metastasis (r = -0.63 for arginine and r = -0.66 for ornithine).DiscussionThese alterations in monocyte amino acid metabolism can reflect the reaction of systemic innate immunity on the growing tumor. Our data indicate that this metabolic programming is cancer specific and can be inhibiting cancer progression. Cancer-specific differences in citrulline, as molecular link between metabolic pathways and epigenetic programing, provide new option for the development and validation of anti-cancer therapies using inhibitors of enzymes catalyzing citrullination. |
| first_indexed | 2024-03-08T16:07:09Z |
| format | Article |
| id | doaj.art-246565c522cc4e35a3507cd87442b9f4 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-08T16:07:09Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-246565c522cc4e35a3507cd87442b9f42024-01-08T04:56:19ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-01-011410.3389/fimmu.2023.13320431332043Specific changes in amino acid profiles in monocytes of patients with breast, lung, colorectal and ovarian cancersVitaliy Chagovets0Natalia Starodubtseva1Natalia Starodubtseva2Alisa Tokareva3Anastasia Novoselova4Marina Patysheva5Marina Patysheva6Irina Larionova7Irina Larionova8Irina Larionova9Elizaveta Prostakishina10Elizaveta Prostakishina11Militsa Rakina12Militsa Rakina13Anna Kazakova14Evgenii Topolnitskiy15Nikolay Shefer16Julia Kzhyshkowska17Julia Kzhyshkowska18Julia Kzhyshkowska19Julia Kzhyshkowska20Vladimir Frankevich21Vladimir Frankevich22Gennadiy Sukhikh23National Medical Research Center for Obstetrics Gynecology and Perinatology Named after Academician V.I. Kulakov of the Ministry of Healthcare of Russian Federation, Moscow, RussiaNational Medical Research Center for Obstetrics Gynecology and Perinatology Named after Academician V.I. Kulakov of the Ministry of Healthcare of Russian Federation, Moscow, RussiaDepartment of Chemical Physics, The Moscow Institute of Physics and Technology, Moscow, RussiaNational Medical Research Center for Obstetrics Gynecology and Perinatology Named after Academician V.I. Kulakov of the Ministry of Healthcare of Russian Federation, Moscow, RussiaNational Medical Research Center for Obstetrics Gynecology and Perinatology Named after Academician V.I. Kulakov of the Ministry of Healthcare of Russian Federation, Moscow, RussiaLaboratory of Translational Cellular And Molecular Biomedicine, National Research Tomsk State University, Tomsk, RussiaCancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, RussiaLaboratory of Translational Cellular And Molecular Biomedicine, National Research Tomsk State University, Tomsk, RussiaCancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, RussiaLaboratory of Genetic Technologies, Siberian State Medical University, Tomsk, RussiaLaboratory of Translational Cellular And Molecular Biomedicine, National Research Tomsk State University, Tomsk, RussiaCancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, RussiaLaboratory of Translational Cellular And Molecular Biomedicine, National Research Tomsk State University, Tomsk, RussiaCancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, RussiaLaboratory of Translational Cellular And Molecular Biomedicine, National Research Tomsk State University, Tomsk, RussiaLaboratory of Genetic Technologies, Siberian State Medical University, Tomsk, RussiaLaboratory of Genetic Technologies, Siberian State Medical University, Tomsk, RussiaLaboratory of Translational Cellular And Molecular Biomedicine, National Research Tomsk State University, Tomsk, RussiaLaboratory of Genetic Technologies, Siberian State Medical University, Tomsk, RussiaInstitute of Transfusion Medicine and Immunology, Mannheim Faculty of Medicine, University of Heidelberg, Heidelberg, GermanyGerman Red Cross Blood Service Baden-Württemberg–Hessen, Mannheim, GermanyNational Medical Research Center for Obstetrics Gynecology and Perinatology Named after Academician V.I. Kulakov of the Ministry of Healthcare of Russian Federation, Moscow, RussiaLaboratory of Translational Medicine, Siberian State Medical University, Tomsk, RussiaNational Medical Research Center for Obstetrics Gynecology and Perinatology Named after Academician V.I. Kulakov of the Ministry of Healthcare of Russian Federation, Moscow, RussiaIntroductionImmunometabolism is essential factor of tumor progression, and tumor-associated macrophages are characterized by substantial changes in their metabolic status. In this study for the first time, we applied targeted amino acid LC-MS/MS analysis to compare amino acid metabolism of circulating monocytes isolated from patients with breast, ovarian, lung, and colorectal cancer.MethodsMonocyte metabolomics was analyzed by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/ MS) analysis of amino acid extracts. The targeted analysis of 26 amino acids was conducted by LCMS/MS on an Agilent 6460 triple quadrupole mass spectrometer equipped with an electrospray ionization source and an Agilent 1260 II liquid chromatograph.ResultsComparison of monocytes of cancer patients with monocytes of healthy control individuals demonstrated that in breast cancer most pronounced changes were identified for tryptophan (AUC = 0.76); for ovarian cancer, aminobutyric acid was significantly elevated (AUC= 1.00); for lung cancer significant changes we indented for citrulline (AUC = 0.70). In order to identify key amino acids that are characteristic for monocytes in specific cancer types, we compared each individual cancer with other 3 types of cancer. We found, that aspartic acid and citrulline are specific for monocytes of patients with colorectal cancer (p<0.001, FC = 1.40 and p=0.003, FC = 1.42 respectively). Citrulline, sarcosine and glutamic acid are ovarian cancer-specific amino acids (p = 0.003, FC = 0.78, p = 0.003, FC = 0.62, p = 0.02, FC = 0.78 respectively). Glutamine, methionine and phenylalanine (p = 0.048, FC = 1.39. p = 0.03, FC = 1.27 and p = 0.02, FC = 1.41) are lung cancer-specific amino acids. Ornithine in monocytes demonstrated strong positive correlation (r = 0.63) with lymph node metastasis incidence in breast cancer patients. Methyl histidine and cysteine in monocytes had strong negative correlation with lymph node metastasis in ovarian cancer patients (r = -0.95 and r = -0.95 respectively). Arginine, citrulline and ornithine have strong negative correlation with tumor size (r = -0.78, citrulline) and lymph node metastasis (r = -0.63 for arginine and r = -0.66 for ornithine).DiscussionThese alterations in monocyte amino acid metabolism can reflect the reaction of systemic innate immunity on the growing tumor. Our data indicate that this metabolic programming is cancer specific and can be inhibiting cancer progression. Cancer-specific differences in citrulline, as molecular link between metabolic pathways and epigenetic programing, provide new option for the development and validation of anti-cancer therapies using inhibitors of enzymes catalyzing citrullination.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1332043/fullmass spectrometrymetabolomicsoncologymonocytestumor-associated macrophages |
| spellingShingle | Vitaliy Chagovets Natalia Starodubtseva Natalia Starodubtseva Alisa Tokareva Anastasia Novoselova Marina Patysheva Marina Patysheva Irina Larionova Irina Larionova Irina Larionova Elizaveta Prostakishina Elizaveta Prostakishina Militsa Rakina Militsa Rakina Anna Kazakova Evgenii Topolnitskiy Nikolay Shefer Julia Kzhyshkowska Julia Kzhyshkowska Julia Kzhyshkowska Julia Kzhyshkowska Vladimir Frankevich Vladimir Frankevich Gennadiy Sukhikh Specific changes in amino acid profiles in monocytes of patients with breast, lung, colorectal and ovarian cancers Frontiers in Immunology mass spectrometry metabolomics oncology monocytes tumor-associated macrophages |
| title | Specific changes in amino acid profiles in monocytes of patients with breast, lung, colorectal and ovarian cancers |
| title_full | Specific changes in amino acid profiles in monocytes of patients with breast, lung, colorectal and ovarian cancers |
| title_fullStr | Specific changes in amino acid profiles in monocytes of patients with breast, lung, colorectal and ovarian cancers |
| title_full_unstemmed | Specific changes in amino acid profiles in monocytes of patients with breast, lung, colorectal and ovarian cancers |
| title_short | Specific changes in amino acid profiles in monocytes of patients with breast, lung, colorectal and ovarian cancers |
| title_sort | specific changes in amino acid profiles in monocytes of patients with breast lung colorectal and ovarian cancers |
| topic | mass spectrometry metabolomics oncology monocytes tumor-associated macrophages |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1332043/full |
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