Cytidine deaminase activity increases in the blood of breast cancer patients.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
18 08 2022
18 08 2022
Historique:
received:
04
01
2022
accepted:
12
08
2022
entrez:
18
8
2022
pubmed:
19
8
2022
medline:
23
8
2022
Statut:
epublish
Résumé
Cytidine deaminase (CDA), an enzyme of the pyrimidine salvage pathway, deaminates cytidine, deoxycytidine and analogs, such as gemcitabine. Constitutive low levels of CDA activity have been reported in the blood of patients with hematological malignancies or suffering from gemcitabine toxicity. We previously reported that cellular CDA deficiency leads to genetic instability. We therefore hypothesized that constitutive CDA deficiency might confer a predisposition to cancer. We analyzed CDA activity and expression in blood samples from breast cancer (BC) patients with a suspected predisposition to the disease, and in healthy controls. Contrary to our hypothesis, we found that both CDA activity and mRNA levels were higher in blood samples from BC patients than in those from controls, and that this difference was not due to excess neutrophils. CDA activity levels were significantly higher in the serum samples of BC patients treated by radiotherapy (RT) than in those of untreated healthy controls, and hormone therapy in RT-treated BC patients was associated with significantly lower levels of CDA activity. A preliminary analysis of CDA activity in the serum of the very few BC patients who had undergone no treatment other than surgery suggested that the increase in CDA activity might be due to the breast cancer itself. Our findings raise important questions, which should lead to studies to elucidate the origin and significance of the increase in CDA activity in the serum of BC patients, and the impact of hormone therapy.
Identifiants
pubmed: 35982128
doi: 10.1038/s41598-022-18462-8
pii: 10.1038/s41598-022-18462-8
pmc: PMC9388666
doi:
Substances chimiques
Hormones
0
Cytidine Deaminase
EC 3.5.4.5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
14062Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2022. The Author(s).
Références
Demontis, S. et al. Isolation and characterization of the gene coding for human cytidine deaminase. Biochim. Biophys. Acta 1443, 323–333. https://doi.org/10.1016/s0167-4781(98)00235-8 (1998).
doi: 10.1016/s0167-4781(98)00235-8
Cacciamani, T. et al. Purification of human cytidine deaminase: Molecular and enzymatic characterization and inhibition by synthetic pyrimidine analogs. Arch. Biochem. Biophys. 290, 285–292. https://doi.org/10.1016/0003-9861(91)90543-r (1991).
doi: 10.1016/0003-9861(91)90543-r
Frances, A. & Cordelier, P. The emerging role of cytidine deaminase in human diseases: A new opportunity for therapy? Mol. Ther. 28, 357–366. https://doi.org/10.1016/j.ymthe.2019.11.026 (2020).
doi: 10.1016/j.ymthe.2019.11.026
Ciccolini, J. et al. Cytidine deaminase residual activity in serum is a predictive marker of early severe toxicities in adults after gemcitabine-based chemotherapies. J. Clin. Oncol. 28, 160–165. https://doi.org/10.1200/JCO.2009.24.4491 (2010).
doi: 10.1200/JCO.2009.24.4491
Nygaard, P. On the role of cytidine deaminase in cellular metabolism. Adv. Exp. Med. Biol. 195(Pt B), 415–420. https://doi.org/10.1007/978-1-4684-1248-2_65 (1986).
doi: 10.1007/978-1-4684-1248-2_65
Chabosseau, P. et al. Pyrimidine pool imbalance induced by BLM helicase deficiency contributes to genetic instability in Bloom syndrome. Nat. Commun. 2, 368. https://doi.org/10.1038/ncomms1363 (2011).
doi: 10.1038/ncomms1363
Gemble, S. et al. Pyrimidine pool disequilibrium induced by a cytidine deaminase deficiency inhibits PARP-1 activity, leading to the under replication of DNA. PLoS Genet. 11, e1005384. https://doi.org/10.1371/journal.pgen.1005384 (2015).
doi: 10.1371/journal.pgen.1005384
Gemble, S. et al. A balanced pyrimidine pool is required for optimal Chk1 activation to prevent ultrafine anaphase bridge formation. J. Cell Sci. 129, 3167–3177. https://doi.org/10.1242/jcs.187781 (2016).
doi: 10.1242/jcs.187781
Gemble, S., Buhagiar-Labarchede, G., Onclercq-Delic, R., Jaulin, C. & Amor-Gueret, M. Cytidine deaminase deficiency impairs sister chromatid disjunction by decreasing PARP-1 activity. Cell Cycle 16, 1128–1135. https://doi.org/10.1080/15384101.2017.1317413 (2017).
doi: 10.1080/15384101.2017.1317413
Silveira, S. C. et al. A decrease in NAMPT activity impairs basal PARP-1 activity in cytidine deaminase deficient-cells, independently of NAD(.). Sci. Rep. 10, 13907. https://doi.org/10.1038/s41598-020-70874-6 (2020).
doi: 10.1038/s41598-020-70874-6
Donnette, M. et al. High incidence of CDA deficiency in patients with hematological malignancies: Perspectives and therapeutic implications. Ann. Oncol. 32, 684–686. https://doi.org/10.1016/j.annonc.2021.01.072 (2021).
doi: 10.1016/j.annonc.2021.01.072
Mahfouz, R. Z. et al. Increased CDA expression/activity in males contributes to decreased cytidine analog half-life and likely contributes to worse outcomes with 5-azacytidine or decitabine therapy. Clin. Cancer Res. 19, 938–948. https://doi.org/10.1158/1078-0432.CCR-12-1722 (2013).
doi: 10.1158/1078-0432.CCR-12-1722
Peters, G. J. et al. Selection of the best blood compartment to measure cytidine deaminase activity to stratify for optimal gemcitabine or cytarabine treatment. Nucleosides Nucleotides Nucleic Acids 33, 403–412. https://doi.org/10.1080/15257770.2014.894196 (2014).
doi: 10.1080/15257770.2014.894196
Helliwell, P. S., Marchesoni, A., Peters, M., Platt, R. & Wright, V. Cytidine deaminase activity, C reactive protein, histidine, and erythrocyte sedimentation rate as measures of disease activity in psoriatic arthritis. Ann. Rheum. Dis. 50, 362–365. https://doi.org/10.1136/ard.50.6.362 (1991).
doi: 10.1136/ard.50.6.362
Cohen, R. et al. Determinants of the interindividual variability in serum cytidine deaminase activity of patients with solid tumours. Br. J. Clin. Pharmacol. 85, 1227–1238. https://doi.org/10.1111/bcp.13849 (2019).
doi: 10.1111/bcp.13849
Wendt, C. & Margolin, S. Identifying breast cancer susceptibility genes—A review of the genetic background in familial breast cancer. Acta Oncol. 58, 135–146. https://doi.org/10.1080/0284186X.2018.1529428 (2019).
doi: 10.1080/0284186X.2018.1529428
Mameri, H. et al. Cytidine deaminase deficiency reveals new therapeutic opportunities against cancer. Clin. Cancer Res. 23, 2116–2126. https://doi.org/10.1158/1078-0432.CCR-16-0626 (2017).
doi: 10.1158/1078-0432.CCR-16-0626
Lavelle, D. et al. Effects of tetrahydrouridine on pharmacokinetics and pharmacodynamics of oral decitabine. Blood 119, 1240–1247. https://doi.org/10.1182/blood-2011-08-371690 (2012).
doi: 10.1182/blood-2011-08-371690
Camiener, G. W. & Smith, C. G. Studies of the enzymatic deamination of cytosine arabinoside. I. Enzyme distribution and species specificity. Biochem. Pharmacol. 14, 1405–1416. https://doi.org/10.1016/0006-2952(65)90175-9 (1965).
doi: 10.1016/0006-2952(65)90175-9
Schernberg, A., Blanchard, P., Chargari, C. & Deutsch, E. Neutrophils, a candidate biomarker and target for radiation therapy? Acta Oncol. 56, 1522–1530. https://doi.org/10.1080/0284186X.2017.1348623 (2017).
doi: 10.1080/0284186X.2017.1348623
Liang, W. & Ferrara, N. The complex role of neutrophils in tumor angiogenesis and metastasis. Cancer Immunol. Res. 4, 83–91. https://doi.org/10.1158/2326-6066.CIR-15-0313 (2016).
doi: 10.1158/2326-6066.CIR-15-0313
Sionov, R. V. Leveling up the controversial role of neutrophils in cancer: When the complexity becomes entangled. Cells 10, 2486. https://doi.org/10.3390/cells10092486 (2021).
doi: 10.3390/cells10092486
Coffelt, S. B., Wellenstein, M. D. & de Visser, K. E. Neutrophils in cancer: Neutral no more. Nat. Rev. Cancer 16, 431–446. https://doi.org/10.1038/nrc.2016.52 (2016).
doi: 10.1038/nrc.2016.52
Ilic, D. et al. Prostate cancer screening with prostate-specific antigen (PSA) test: A systematic review and meta-analysis. BMJ 362, k3519. https://doi.org/10.1136/bmj.k3519 (2018).
doi: 10.1136/bmj.k3519
Mercier, C. et al. Toxic death case in a patient undergoing gemcitabine-based chemotherapy in relation with cytidine deaminase downregulation. Pharmacogenet. Genomics 17, 841–844. https://doi.org/10.1097/FPC.0b013e32825ea6e3 (2007).
doi: 10.1097/FPC.0b013e32825ea6e3
Bieche, I. et al. Quantification of estrogen receptor alpha and beta expression in sporadic breast cancer. Oncogene 20, 8109–8115. https://doi.org/10.1038/sj.onc.1204917 (2001).
doi: 10.1038/sj.onc.1204917
Sekhon, J. S. Multivariate and propensity score matching software with automated balance optimization: The matching package for R. J. Stat. Softw. 42, 1–52. https://doi.org/10.18637/jss.v042.i07 (2011).
doi: 10.18637/jss.v042.i07