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      UHPLC-ESI-MS/MS Quantification of Relevant Substrates and Metabolites of the Kynurenine Pathway Present in Serum and Peritoneal Fluid from Gastric Cancer Patients—Method Development and Validation

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          Abstract

          Metabolites and enzymes involved in the kynurenine pathway (KP) are highly promising targets for cancer treatment, including gastrointestinal tract diseases. Thus, accurate quantification of these compounds in body fluids becomes increasingly important. The aim of this study was the development and validation of the UHPLC-ESI-MS/MS methods for targeted quantification of biologically important KP substrates (tryptophan and nicotinamide) and metabolites(kynurenines) in samples of serum and peritoneal fluid from gastric cancer patients. The serum samples were simply pretreated with trichloroacetic acid to precipitate proteins. The peritoneal fluid was purified by solid-phase extraction before analysis. Validation was carried out for both matrices independently. Analysis of the samples from gastric cancer patients showed different accumulations of tryptophan and its metabolites in different biofluids of the same patient. The protocols will be used for the evaluation of tryptophan and kynurenines in blood and peritoneal fluid to determine correlation with the clinicopathological status of gastric cancer or the disease’s prognosis.

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          Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

          Ahmedin Jemal, Lindsey A Torre, Rebecca Siegel … (2018)
          This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.
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            Gastric cancer

            Elizabeth Smyth, Magnus Nilsson, Heike I Grabsch … (2020)
            Gastric cancer is the fifth most common cancer and the third most common cause of cancer death globally. Risk factors for the condition include Helicobacter pylori infection, age, high salt intake, and diets low in fruit and vegetables. Gastric cancer is diagnosed histologically after endoscopic biopsy and staged using CT, endoscopic ultrasound, PET, and laparoscopy. It is a molecularly and phenotypically highly heterogeneous disease. The main treatment for early gastric cancer is endoscopic resection. Non-early operable gastric cancer is treated with surgery, which should include D2 lymphadenectomy (including lymph node stations in the perigastric mesentery and along the celiac arterial branches). Perioperative or adjuvant chemotherapy improves survival in patients with stage 1B or higher cancers. Advanced gastric cancer is treated with sequential lines of chemotherapy, starting with a platinum and fluoropyrimidine doublet in the first line; median survival is less than 1 year. Targeted therapies licensed to treat gastric cancer include trastuzumab (HER2-positive patients first line), ramucirumab (anti-angiogenic second line), and nivolumab or pembrolizumab (anti-PD-1 third line).
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              Cancer incidence and mortality patterns in Europe: Estimates for 40 countries and 25 major cancers in 2018

              J Ferlay, M Colombet, I Soerjomataram … (2018)
              Europe contains 9% of the world population but has a 25% share of the global cancer burden. Up-to-date cancer statistics in Europe are key to cancer planning. Cancer incidence and mortality estimates for 25 major cancers are presented for the 40 countries in the four United Nations-defined areas of Europe and for Europe and the European Union (EU-28) for 2018.
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                Author and article information

                Contributors
                Claudiu T. Supuran: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): Int J Mol Sci
                Journal ID (iso-abbrev): Int J Mol Sci
                Journal ID (publisher-id): ijms
                Title: International Journal of Molecular Sciences
                Publisher: MDPI
                ISSN (Electronic): 1422-0067
                Publication date (Electronic): 28 June 2021
                Publication date Collection: July 2021
                Volume: 22
                Issue: 13
                Electronic Location Identifier: 6972
                Affiliations
                [1 ]Laboratory of Separation and Spectroscopic Method Applications, Centre for Interdisciplinary Research, Faculty of Science and Health, The John Paul II Catholic University of Lublin, Konstantynów 1J, 20-708 Lublin, Poland; ilona.sadok@ 123456kul.pl (I.S.); k.jedruchniewicz@ 123456umcs.pl (K.J.)
                [2 ]Department of Surgical Oncology, Medical University of Lublin, Radziwiłłowska 13, 20-080 Lublin, Poland; karolrawiczpruszynski@ 123456uml.edu.pl
                Author notes
                [* ]Correspondence: magdalena.staniszewska@ 123456kul.pl ; Tel.: +48-81-454-56-21
                Author information
                https://orcid.org/0000-0003-1154-7581
                https://orcid.org/0000-0003-3945-7377
                https://orcid.org/0000-0003-1119-2397
                Article
                Publisher ID: ijms-22-06972
                DOI: 10.3390/ijms22136972
                PMC ID: 8269001
                PubMed ID: 34203517
                SO-VID: 12595166-af40-4fd1-9423-f163c9c1c45e
                Copyright © © 2021 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 08 June 2021
                Date accepted : 24 June 2021
                Categories
                Subject: Article

                ScienceOpen disciplines: Molecular biology
                Keywords: tryptophan metabolism,kynurenine pathway,gastric cancer,targeted metabolomics,lc-ms/ms,serum analysis,peritoneal fluid analysis
                Data availability:
                ScienceOpen disciplines: Molecular biology
                Keywords: tryptophan metabolism, kynurenine pathway, gastric cancer, targeted metabolomics, lc-ms/ms, serum analysis, peritoneal fluid analysis

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