Online first
Current issue
Archive
Special Issues
About the Journal
Publication Ethics
Anti-Plagiarism system
Instructions for Authors
Instructions for Reviewers
Editorial Board
Editorial Office
Contact
Reviewers
All Reviewers
2023
2022
2021
2020
2019
2018
2017
2016
General Data Protection Regulation (RODO)
RESEARCH PAPER
Surgical resection of lung cancer inhibits mRNA expression of GOT2 gene encoding kynurenine aminotransferase in leukocytes
1
Thoracic Surgery Department, Medical University, Lublin, Poland
2
Department of Clinical Genetics, Medical University, Lublin, Poland
3
Department of Clinical Genetics, Medical University in Lublin., Poland
Corresponding author
Ann Agric Environ Med. 2023;30(4):755-762
KEYWORDS
TOPICS
ABSTRACT
Introduction and objective:
Lung cancer is the most common malignant tumour. More than 80% of all diagnosed cases are non-small cell carcinoma which can be effectively treated by radical resection. Despite significant progress in the field of diagnostic and therapeutic methods, the results of lung cancer treatment are still unsatisfactory. Lung cancer is detected relatively late, which leads to an unfavourable prognosis. Kynurenine aminotransferases are an important element of the kynurenine pathway of tryptophan metabolism, which has recently aroused great interest from the aspect of possible use as a target point of personalized therapies in malignant tumours.The aim of the study was to analyze the expression of the selected gene of kynurenine aminotransferases GOT 2 at the mRNA level in peripheral blood leukocytes of patients with lung cancer.
Material and methods:
The mRNA expression of the GOT 2 gene was tested on blood samples from 50 patients treated surgically for non-small cell lung cancer.The control group consisted of 15 healthy individuals.The determination of mRNA expression of the GOT 2 gene was performed using the real-time PCR method.The GAPDH gene was used as the endogenous reference level.
Results:
The mRNA expression of the GOT2 gene on the 6th day after surgery was statistically significantly lower than before surgery (p = 0,05). In the study group, the average LogRQ mRNA expression of the GOT2 gene before the procedure was 0.192082±0.292174 in woman. This was statistically significantly higher than in men whose average LogRQ mRNA expression of the GOT2 gene before the procedure was 0.004210±0.235065 (p=0.0183).
Conclusions:
Surgical resection of lung cancer results in inhibition of GOT2 mRNA expression in leukocytes. Further studies are expected to show whether it may be used as a target point for personalized therapies in lung cancer.
Lung cancer is the most common malignant tumour. More than 80% of all diagnosed cases are non-small cell carcinoma which can be effectively treated by radical resection. Despite significant progress in the field of diagnostic and therapeutic methods, the results of lung cancer treatment are still unsatisfactory. Lung cancer is detected relatively late, which leads to an unfavourable prognosis. Kynurenine aminotransferases are an important element of the kynurenine pathway of tryptophan metabolism, which has recently aroused great interest from the aspect of possible use as a target point of personalized therapies in malignant tumours.The aim of the study was to analyze the expression of the selected gene of kynurenine aminotransferases GOT 2 at the mRNA level in peripheral blood leukocytes of patients with lung cancer.
Material and methods:
The mRNA expression of the GOT 2 gene was tested on blood samples from 50 patients treated surgically for non-small cell lung cancer.The control group consisted of 15 healthy individuals.The determination of mRNA expression of the GOT 2 gene was performed using the real-time PCR method.The GAPDH gene was used as the endogenous reference level.
Results:
The mRNA expression of the GOT2 gene on the 6th day after surgery was statistically significantly lower than before surgery (p = 0,05). In the study group, the average LogRQ mRNA expression of the GOT2 gene before the procedure was 0.192082±0.292174 in woman. This was statistically significantly higher than in men whose average LogRQ mRNA expression of the GOT2 gene before the procedure was 0.004210±0.235065 (p=0.0183).
Conclusions:
Surgical resection of lung cancer results in inhibition of GOT2 mRNA expression in leukocytes. Further studies are expected to show whether it may be used as a target point for personalized therapies in lung cancer.
REFERENCES (31)
1.
Travis WD, Brambilla E, Nicholson AG, et al. The 2015 World Health Organization Classification of Lung Tumors. J Thorac Oncol. 2015;10(9):1243–1260.
2.
Jassem J. Nowotwory płuca i opłucnej. In: Interna Szczeklika: Podręcznik chorób wewnętrznych 2018. Kraków: Medycyna Praktyczna; 2018, p. 800–830.
3.
Yoo JW,Seo KW, Jang SJ, Oh YM, Shim TS, Kim WS, Lee DS, Lee SD, Choi CM. The relationship between the presence of chromosomal instability and prognosis of squamous cell carcinoma of the lung: fluorescencje in situ hybridization analysis of paraffin- embedded tissue from 47 korean patients. J Korean Med Sci. 2010;25(6):863.
4.
Zuin A, Marulli G, Breda C, Bulf R, Schiavon M, Rebusso A, Di Chiara F, Rea F. Pneumonectomy for lung cancer over the age of 75 years: is it worthwhile? Interact Cardiovasc Thorac Surg. 2010;10:931–935.
5.
Detterbeck F. The eighth edition TNM stage classification for lung cancer: What does it mean on main street? J Thorac Cardiovasc Surg. 2018;155(1):356–359.
6.
Okada A, Hirono T, Watanabe T. Safety and prognosis of limited surgery for octogenarians with non-small-cell lung cancer. Gen Thorac Cardiovasc Surg. 2012;60:97–103.
7.
Kruk A, Książek J. Analiza jakości życia chorych operowanych na raka płuca. Problemy Pielęgniarstwa. 2017;25(3):161–167.
8.
Ayabe T, Tomita M, Nose N, Asada T, Nakamura K. Patient-Reported Outcomes of Surgery of Non-Small Cell Lung Cancer: Evaluation Based on the Questionnaires of Anti-Aging Quality of Life and the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire. Surgical Sci. 2017;8:203–219.
9.
Mainini C, Rebelo P, Bardelli R, Kopliku B, Tenconi S, Costi S, Tedeschi C, Fugazzaro S. Perioperative physical exercise interventions for patients undergoing lung cancer surgery: What is the evidence? SAGE Open Med. 2016;4:1–19.
10.
Westergaard N, Drejer J, Schousboe A, Sonnewald U. Evaluation of the importance of transamination versus deamination in astrocytic metabolism of [U-13C]glutamate. Glia. 1996;17(2):160–168.
11.
Schousboe A, Westergaard N, Sonnewald U, Petersen SB, Huang R, Peng L, Hertz L. Glutamate and glutamine metabolism and compartmentation in astrocytes. Dev Neurosci. 1993;15:359–366.
12.
Kozłowski P, Kozłowska M, Kozłowska K. Effects of kynurenic acid on cardiovascular system. J Educ Health Sport. 2017;7(8):525–536.
13.
Pedersen ER, Tuseth N, Eussen SJ, Ueland PM, Strand E, Svingen GF, Midttun O, Meyer K, Mellgren G, Ulvik A, Nordrehaug JE, Nilsen DW, Nygard O: Associations of plasma kynurenines with risk of acute myocardial infarction in patients with stable angina pectoris. Arterioscler Thromb Vasc Biol. 2015;35(2):455–62.
14.
Borst P. The malate-aspartate shuttle (Borst cycle): how it started and developed into a major metabolic pathway. IUBMB Life. 2020;72(11):2241–2259.
15.
Birsoy K, Wang T, Chen WW, Freinkman E, Abu-Remaileh M, Sabatini DM. An essential role of the mitochondrial electron transport chain in cell proliferation is to enable aspartate synthesis. Cell. 2015;162(3):540–551.
16.
Garcia-Bermudez J, Baudrier L, La K, et al. Aspartate is a limiting metabolite for cancer cell proliferation under hypoxia and in tumours. Nat Cell Biol. 2018;20(7):775–781.
17.
Sullivan LB, Gui DY, Hosios AM, Bush LN, Freinkman E, Vander Heiden MG. Supporting aspartate biosynthesis is an essential function of respiration in proliferating cells. Cell. 2015;162(3):552–563.
18.
Sullivan LB, Luengo A, Danai LV, et al. Aspartate is an endogenous metabolic limitation for tumour growth. Nat Cell Biol. 2018;20(7):782–788.
19.
Kerk S, Garcia-Bermudez J, Birsoy K, Sherman M, Shah Y, Lyssiotis C. Spotlight on GOT2 in Cancer Metabolism. Onco Targets Ther. 2023;16: 695–702.
20.
Heather LC, Cole MA, Lygate CA, et al. Fatty acid transporter levels and palmitate oxidation rate correlate with ejection fraction in the infarcted rat heart. Cardiovasc Res. 2006;72(3):430–437.
21.
Kalinowska A, Górski J, Harasim E, Harasiuk D, Bonen A, Chabowski A. Differential effects of chronic, in vivo, PPAR’s stimulation on the myocardial subcellular redistribution of FAT/CD36 and FABPpm. FEBS Lett. 2009;583(15):2527–2534.
22.
Abrego J, Sanford-Crane H, Oon C, et al. A cancer cell-intrinsic GOT2-PPARd axis suppresses antitumor immunity. Cancer Discov. 2022;12(10):2414–2433.
23.
Li Y, Li B, Xu Y, et al. GOT2 silencing promotes reprogramming of glutamine metabolism and sensitizes hepatocellular carcinoma to glutaminase inhibitors. Cancer Res. 2022;82(18):3223–3235.
24.
Du F, Chen J, Liu H, et al. SOX12 promotes colorectal cancer cell proliferation and metastasis by regulating asparagine synthesis. Cell Death Dis. 2019;10(3):239.
25.
Mori Y, Mouri A, Kunisawa K, Hirakawa M, Kubota H, Kosuge A, Niijima M, Hasegawa M, Kurahashi H, Murakami R, Hoshi M, Nakano T, Fujigaki S, Fujigaki H, Yamamoto Y, Nabeshima T, Saito K. Kynurenine 3-monooxygenase deficiency induces depression-like behavior via enhanced antagonism of ?7 nicotinic acetylcholine receptors by kynurenic acid. Behav Brain Res. 2021;405:113–191.
26.
Dudzińska E, Szymona K, Kloc R, Kocki T, Gil-Kulik P, Bogucki J, Kocki J, Paduch R, Urbańska E. Fractalkine, sICAM-1 and Kynurenine Pathway in Restrictive Anorexia Nervosa–Exploratory Study. Nutrients. 2021;13(2):339.
27.
Dudzińska E, Szymona K, Kloc R, Gil-Kulik P, Kocki T, Świstowska M, Bogucki J, Kocki J, Urbanska E. Increased expression of kynurenineaminotransferases mRNA in lymphocytes of patients with inflammatory bowel disease. Ther Adv Gastroenterol. 2019;12:1–14.
28.
Kindler J. Lim Ch, Shannon Weickert C, Boerrigter D, Galletly Ch, Liu D, Jacobs K, Balzan R, Bruggemann J, O’Donnell M, Lenroot R, Guillemin G, Weickert T. Dysregulation of kynurenine metabolism is related to proinflammatory cytokines, attention, and prefrontal cortex volume in schizophrenia. Mol Psychiatry. 2020;25(11):2860–2872.
29.
Matysik-Woźniak A, Jünemann A, Turski W, Wnorowski A, Jóźwiak K, Paduch R, Okuno E, Moneta-Wielgoś J, Chorągiewicz T, Maciejewski R, Rejdak R. The presence of kynurenine aminotransferases in the human cornea: Evidence from bioinformatics analysis of gene expression and immunohistochemical staining. Molecular Vision. 2017;23:364–371.
30.
Zhang R, Li H,Yu J, Zhao J, Wang X, Wang G, Yao Z, Wei F, Xue Q, Ren X. Immunoactivative role of indoleamine 2,3 dioxygenase in gastric cancer cells in vitro. Mol Med Rep. 2011;4(1):169–73.
31.
Sagan D, Kocki T, Patel S, Kocki J. Utility of Kynurenic Acid for Non-Invasive Detection of Metastatic Spread to Lymph Nodes in NonSmall Cell Lung Cancer. J Med Sci. 2015;12:146–153.
| eISSN: | 1898-2263 |
| ISSN: | 1232-1966 |
Improvement of visual identification of the journal - task financed under the agreement No. 618/P-DUN/2019 by the Minister of Science and Higher Education allocated to the activities of disseminating science.
Generation of the DOI (Digital Object Identifier) - task financed under the agreement No. 618/P-DUN/2019 by the Minister of Science and Higher
© 2006-2024 Journal hosting platform by Bentus
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
