{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T01:50:25Z","timestamp":1764813025691,"version":"build-2065373602"},"reference-count":63,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T00:00:00Z","timestamp":1669939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Associaci\u00f3 Oncol\u00f2gica Dr. Amadeu Pelegr\u00ed","award":["AODAP\/2019","AODAP\/2020"],"award-info":[{"award-number":["AODAP\/2019","AODAP\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Radiotherapy (RT) is part of the standard treatment of breast cancer (BC) because of its effects on relapse reduction and survival. However, response to treatment is highly variable, and some patients may develop disease progression (DP), a second primary cancer, or may succumb to the disease. Antioxidant systems and inflammatory processes are associated with the onset and development of BC and play a role in resistance to treatment. Here, we report our investigation into the clinical evolution of BC patients, and the impact of RT on the circulating levels of the antioxidant enzyme paraoxonase-1 (PON1), cytokines, and other standard biochemical and hematological variables. Gradient Boosting Machine (GBM) algorithm was used to identify predictive variables. This was a retrospective study in 237 patients with BC. Blood samples were obtained pre- and post-RT, with samples of healthy women used as control subjects. Results showed that 24 patients had DP eight years post-RT, and eight patients developed a second primary tumor. The algorithm identified interleukin-4 and total lymphocyte counts as the most relevant indices discriminating between BC patients and control subjects, while neutrophils, total leukocytes, eosinophils, very low-density lipoprotein cholesterol, and PON1 activity were potential predictors of fatal outcome.<\/jats:p>","DOI":"10.3390\/antiox11122394","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T03:38:38Z","timestamp":1670211518000},"page":"2394","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Gradient Boosting Machine Identified Predictive Variables for Breast Cancer Patients Pre- and Post-Radiotherapy: Preliminary Results of an 8-Year Follow-Up Study"],"prefix":"10.3390","volume":"11","author":[{"given":"Elisabet","family":"Rodr\u00edguez-Tom\u00e0s","sequence":"first","affiliation":[{"name":"Unitat de Recerca Biom\u00e8dica, Hospital Universitari de Sant Joan, Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili, Universitat Rovira i Virgili, 43201 Reus, Spain"},{"name":"Department of Radiation Oncology, Hospital Universitari de Sant Joan, Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili, Universitat Rovira i Virgili, 43204 Reus, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0815-2570","authenticated-orcid":false,"given":"Meritxell","family":"Arenas","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Hospital Universitari de Sant Joan, Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili, Universitat Rovira i Virgili, 43204 Reus, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerard","family":"Baiges-Gaya","sequence":"additional","affiliation":[{"name":"Unitat de Recerca Biom\u00e8dica, Hospital Universitari de Sant Joan, Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili, Universitat Rovira i Virgili, 43201 Reus, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johana","family":"Acosta","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Hospital Universitari de Sant Joan, Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili, Universitat Rovira i Virgili, 43204 Reus, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo","family":"Araguas","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Hospital Universitari de Sant Joan, Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili, Universitat Rovira i Virgili, 43204 Reus, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e1rbara","family":"Malave","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Hospital Universitari de Sant Joan, Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili, Universitat Rovira i Virgili, 43204 Reus, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8786-7368","authenticated-orcid":false,"given":"Helena","family":"Casta\u00f1\u00e9","sequence":"additional","affiliation":[{"name":"Unitat de Recerca Biom\u00e8dica, Hospital Universitari de Sant Joan, Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili, Universitat Rovira i Virgili, 43201 Reus, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4251-585X","authenticated-orcid":false,"given":"Andrea","family":"Jim\u00e9nez-Franco","sequence":"additional","affiliation":[{"name":"Unitat de Recerca Biom\u00e8dica, Hospital Universitari de Sant Joan, Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili, Universitat Rovira i Virgili, 43201 Reus, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roc\u00edo","family":"Benavides-Villarreal","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Hospital Universitari de Sant Joan, Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili, Universitat Rovira i Virgili, 43204 Reus, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebasti\u00e0","family":"Sabater","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Hospital Universitari de Sant Joan, Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili, Universitat Rovira i Virgili, 43204 Reus, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa","family":"Sol\u00e0-Alberich","sequence":"additional","affiliation":[{"name":"Functional Nutrition, Oxidation and Cardiovascular Disease Group (NFOC-SALUT), Facultat de Medicina i Ci\u00e8ncies de La Salut, Universitat Rovira i Virgili, 43201 Reus, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3165-3640","authenticated-orcid":false,"given":"Jordi","family":"Camps","sequence":"additional","affiliation":[{"name":"Unitat de Recerca Biom\u00e8dica, Hospital Universitari de Sant Joan, Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili, Universitat Rovira i Virgili, 43201 Reus, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2749-4541","authenticated-orcid":false,"given":"Jorge","family":"Joven","sequence":"additional","affiliation":[{"name":"Unitat de Recerca Biom\u00e8dica, Hospital Universitari de Sant Joan, Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili, Universitat Rovira i Virgili, 43201 Reus, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/nrclinonc.2015.73","article-title":"Clinical management of breast cancer heterogeneity","volume":"12","author":"Zardavas","year":"2015","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s10549-016-3757-4","article-title":"Risk of regional recurrence in triple-negative breast cancer patients: A Dutch cohort study","volume":"156","author":"Smit","year":"2016","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1148\/radiol.2017162348","article-title":"Breast Cancer Detected at Screening US: Survival Rates and Clinical-Pathologic and Imaging Factors Associated with Recurrence","volume":"284","author":"Kim","year":"2017","journal-title":"Radiology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1053\/j.seminoncol.2020.05.003","article-title":"Novel radiation therapy approaches for breast cancer treatment","volume":"47","author":"Shah","year":"2020","journal-title":"Semin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2382","DOI":"10.1200\/JCO.2012.45.2615","article-title":"Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: Long-term follow-up of CALGB 9343","volume":"31","author":"Hughes","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/S1470-2045(14)71221-5","article-title":"Breast-conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer (PRIME II): A randomised controlled trial","volume":"16","author":"Kunkler","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5463","DOI":"10.1002\/cncr.27581","article-title":"Clinicopathologic features, patterns of recurrence, and survival among women with triple-negative breast cancer in the National Comprehensive Cancer Network","volume":"15","author":"Lin","year":"2012","journal-title":"Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/s41568-020-0266-x","article-title":"Key steps for effective breast cancer prevention","volume":"20","author":"Britt","year":"2020","journal-title":"Nat. Rev. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Camps, J., Casta\u00f1\u00e9, H., Rodr\u00edguez-Tom\u00e0s, E., Baiges-Gaya, G., Hern\u00e1ndez-Aguilera, A., Arenas, M., Iftimie, S., and Joven, J. (2021). On the role of paraoxonase-1 and chemokine ligand 2 (c-c motif) in metabolic alterations linked to inflammation and disease. A 2021 update. Biomolecules, 11.","DOI":"10.20944\/preprints202106.0023.v1"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1016\/j.freeradbiomed.2010.09.006","article-title":"Oxidative stress, inflammation, and cancer: How are they linked?","volume":"49","author":"Reuter","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.critrevonc.2018.04.005","article-title":"Paraoxonase-1 activity in patients with cancer: A systematic review and meta-analysis","volume":"127","author":"Arenas","year":"2018","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Arenas, M., Garc\u00eda-Heredia, A., Cabr\u00e9, N., Luciano-Mateo, F., Hern\u00e1ndez-Aguilera, A., Sabater, S., Bonet, M., Gasc\u00f3n, M., Fern\u00e1ndez-Arroyo, S., and Fort-Gallifa, I. (2017). Effect of radiotherapy on activity and concentration of serum paraoxonase-1 in breast cancer patients. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0188633"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"103605","DOI":"10.1016\/j.jprot.2019.103605","article-title":"Alterations in plasma concentrations of energy-balance-related metabolites in patients with lung, or head & neck, cancers: Effects of radiotherapy","volume":"213","author":"Arenas","year":"2020","journal-title":"J. Proteom."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Tom\u00e0s, E., Arenas, M., G\u00f3mez, J., Acosta, J., Trilla, J., L\u00f3pez, Y., \u00c1rquez, M., Torres, L., Araguas, P., and Hern\u00e1ndez-Aguilera, A. (2021). Identification of potential metabolic biomarkers of rectal cancer and of the effect of neoadjuvant radiochemotherapy. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0250453"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1080\/10408360802610878","article-title":"The paraoxonases: Role in human diseases and methodological difficulties in measurement","volume":"46","author":"Camps","year":"2009","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.hemonc.2021.02.002","article-title":"Molecular mediators of breast cancer metastasis","volume":"14","author":"Yeeravalli","year":"2021","journal-title":"Hematol. Oncol. Stem Cell. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e47575","DOI":"10.15252\/embr.201847575","article-title":"The emerging roles of inflammasome-dependent cytokines in cancer development","volume":"20","author":"Lamkanfi","year":"2019","journal-title":"EMBO Rep."},{"key":"ref_19","first-page":"11","article-title":"Tumor-induced inflammatory cytokines and the emerging diagnostic devices for cancer detection and prognosis","volume":"7","author":"Kartikasari","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1089\/jir.2018.0087","article-title":"The interferon-gamma paradox in cancer","volume":"39","author":"Zaidi","year":"2019","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ganggayah, M.D., Taib, N.A., Har, Y.C., Lio, P., and Dhillon, S.K. (2019). Predicting factors for survival of breast cancer patients using machine learning techniques. BMC Med. Inform. Decis. Mak., 19.","DOI":"10.1186\/s12911-019-0801-4"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/s41586-021-04278-5","article-title":"Multi-omic machine learning predictor of breast cancer therapy response","volume":"601","author":"Sammut","year":"2022","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijmedinf.2017.09.013","article-title":"Prediction of lung cancer patient survival via supervised machine learning classification techniques","volume":"108","author":"Lynch","year":"2017","journal-title":"Int. J. Med. Inform."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"152","DOI":"10.21037\/atm.2019.03.29","article-title":"Predictive analytics with gradient boosting in clinical medicine","volume":"7","author":"Zhang","year":"2019","journal-title":"Ann. Transl. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1136\/gutjnl-2020-321799","article-title":"Development and validation of a model to predict survival in colorectal cancer using a gradient-boosted machine","volume":"70","author":"Bibault","year":"2021","journal-title":"Gut"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ji, G.W., Jiao, C.Y., Xu, Z.G., Li, X.C., Wang, K., and Wang, X.H. (2022). Development and validation of a gradient boosting machine to predict prognosis after liver resection for intrahepatic cholangiocarcinoma. BMC Cancer, 22.","DOI":"10.1186\/s12885-022-09352-3"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3539","DOI":"10.1200\/JCO.2001.19.15.3539","article-title":"A simple stratification factor prognostic for survival in advanced cancer: The good\/bad\/uncertain index","volume":"19","author":"Sloan","year":"2001","journal-title":"J. Clin. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.breast.2014.01.011","article-title":"Accelerated hypofractionated breast radiotherapy: FAQs (Frequently Asked Questions) and facts","volume":"23","author":"Montero","year":"2014","journal-title":"Breast"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.radonc.2017.01.014","article-title":"Understanding variations in the use of hypofractionated radiotherapy and its specific indications for breast cancer: A mixed-methods study","volume":"123","author":"Prades","year":"2017","journal-title":"Radiother. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1007\/s12094-015-1401-0","article-title":"The position and current status of radiation therapy after primary systemic therapy in breast cancer: A national survey-based expert consensus statement","volume":"18","author":"Arenas","year":"2016","journal-title":"Clin. Translat. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1002\/hed.24733","article-title":"Reirradiation of head and neck cancer: Long-term disease control and toxicity","volume":"39","author":"Bots","year":"2017","journal-title":"Head Neck"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1007\/s00277-010-0901-9","article-title":"Effects of C282Y, H63D, and S65C HFE gene mutations, diet, and life-style factors on iron status in a general Mediterranean population from Tarragona, Spain","volume":"89","author":"Aranda","year":"2010","journal-title":"Ann. Hematol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1161\/01.ATV.21.4.542","article-title":"Human paraoxonase-3 is an hdl-associated enzyme with biological activity similar to paraoxonase-1 protein but is not regulated by oxidized lipids","volume":"21","author":"Reddy","year":"2001","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.neunet.2021.04.030","article-title":"Generalized two-dimensional linear discriminant analysis with regularization","volume":"142","author":"Li","year":"2021","journal-title":"Neural Netw."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2872","DOI":"10.1038\/s41467-021-23102-2","article-title":"Supervised dimensionality reduction for big data","volume":"12","author":"Vogelstein","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3389\/fninf.2014.00014","article-title":"Machine learning for neuroimaging with scikit-learn","volume":"8","author":"Abraham","year":"2014","journal-title":"Front. Neuroinform."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1002\/ijc.31914","article-title":"Ten-year recurrence rates for breast cancer subtypes in the Netherlands: A large population-based study","volume":"144","author":"Strobbe","year":"2019","journal-title":"Int. J. Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.semradonc.2011.12.001","article-title":"Predictive factors for local recurrence in breast cancer","volume":"22","author":"Elkhuizen","year":"2012","journal-title":"Semin. Radiat. Oncol."},{"key":"ref_39","first-page":"e13038","article-title":"Factors influencing breast cancer outcomes in Australia: A systematic review","volume":"28","author":"Tran","year":"2019","journal-title":"Eur. J. Cancer Care"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1007\/s00268-006-0097-2","article-title":"Breast cancer local recurrence: Risk factors and prognostic relevance of early time to recurrence","volume":"31","author":"Neri","year":"2007","journal-title":"World J. Surg."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1002\/jbmr.3618","article-title":"Understanding the bone in cancer metastasis","volume":"33","author":"Fornetti","year":"2018","journal-title":"J. Bone Miner. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/978-3-030-20301-6_7","article-title":"Bone metastasis of breast cancer","volume":"1152","author":"Tahara","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.bone.2010.05.007","article-title":"The bone remodeling environment is a factor in breast cancer bone metastasis","volume":"48","author":"Ooi","year":"2011","journal-title":"Bone"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"104171","DOI":"10.1016\/j.compbiomed.2020.104171","article-title":"Development of an absolute assignment predictor for triple-negative breast cancer subtyping using machine learning approaches","volume":"129","author":"Michel","year":"2021","journal-title":"Comput. Biol. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/978-3-030-78775-2_3","article-title":"Decision Support System for Breast Cancer Detection Using Biomarker Indicators","volume":"1338","author":"Vergis","year":"2021","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"944569","DOI":"10.3389\/fonc.2022.944569","article-title":"A machine learning model based on ultrasound image features to assess the risk of sentinel lymph node metastasis in breast cancer patients: Applications of scikit-learn and SHAP","volume":"12","author":"Zhang","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_47","first-page":"6968","article-title":"Explainable machine learning can outperform Cox regression predictions and provide insights in breast cancer survival","volume":"26","author":"Hendriks","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1007\/s00330-021-08271-4","article-title":"Predicting the molecular subtype of breast cancer and identifying interpretable imaging features using machine learning algorithms","volume":"32","author":"Ma","year":"2022","journal-title":"Eur. Radiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1038\/nrc2507","article-title":"Cytokines and their relationship to the symptoms and outcome of cancer","volume":"8","author":"Seruga","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Carty, S.A., Koretzky, G.A., and Jordan, M.S. (2014). Interleukin-4 regulates eomesodermin in cd8+ t cell development and differentiation. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0106659"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4022","DOI":"10.1158\/0008-5472.CAN-07-6874","article-title":"Crucial role of interleukin-4 in the survival of colon cancer stem cells","volume":"68","author":"Francipane","year":"2008","journal-title":"Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1007\/s00262-017-2043-6","article-title":"IL-4 blockade alters the tumor microenvironment and augments the response to cancer immunotherapy in a mouse model","volume":"66","author":"Ito","year":"2017","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"C\u00e1rdenas, D.M., S\u00e1nchez, A.C., Rosas, D.A., Rivero, E., Paparoni, M.D., Cruz, M.A., Su\u00e1rez, Y.P., and Galvis, N.F. (2018). Preliminary analysis of single-nucleotide polymorphisms in IL-10, IL-4, and IL-4R\u03b1 genes and profile of circulating cytokines in patients with gastric cancer. BMC Gastroenterol., 18.","DOI":"10.1186\/s12876-018-0913-9"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Bednarz-Misa, I., Diakowska, D., Szczuka, I., Fortuna, P., Kubiak, A., Rosi\u0144czuk, J., and Krzystek-Korpacka, M. (2020). Interleukins 4 and 13 and their receptors are differently expressed in gastrointestinal tract cancers, depending on the anatomical site and disease advancement, and improve colon cancer cell viability and motility. Cancers, 12.","DOI":"10.3390\/cancers12061463"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e1457598","DOI":"10.1080\/2162402X.2018.1457598","article-title":"Serum cytokine levels in breast cancer patients during neoadjuvant treatment with bevacizumab","volume":"7","author":"Jabeen","year":"2018","journal-title":"OncoImmunology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1002\/1097-0142(197601)37:1<164::AID-CNCR2820370123>3.0.CO;2-H","article-title":"The prognostic significance of peripheral lymphocyte counts in patients with breast carcinoma","volume":"37","author":"Papatestas","year":"1976","journal-title":"Cancer"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"13203","DOI":"10.1038\/s41598-020-70077-z","article-title":"Neutrophil to lymphocyte ratio and breast cancer risk: Analysis by subtype and potential interactions","volume":"10","author":"Matabuena","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.2147\/CMAR.S292048","article-title":"Lymphocyte-to-monocyte ratio is associated with the poor prognosis of breast cancer patients receiving neoadjuvant chemotherapy","volume":"13","author":"Ma","year":"2021","journal-title":"Cancer Manag. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1186\/s13045-021-01187-y","article-title":"Neutrophils in cancer carcinogenesis and metastasis","volume":"14","author":"Xiong","year":"2021","journal-title":"J. Hematol. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.canlet.2020.10.015","article-title":"Targeting neutrophil extracellular traps with thrombomodulin prevents pancreatic cancer metastasis","volume":"497","author":"Kajioka","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1016\/j.clinbiochem.2017.04.016","article-title":"Paraoxonases and infectious diseases","volume":"50","author":"Camps","year":"2017","journal-title":"Clin. Biochem."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Tom\u00e0s, E., Murcia, M., Arenas, M., Argu\u00eds, M., Gil, M., Amig\u00f3, N., Correig, X., Torres, L., Sabater, S., and Baiges-Gay\u00e0, G. (2019). Serum paraoxonase-1-related variables and lipoprotein profile in patients with lung or head and neck cancer: Effect of radiotherapy. Antioxidants, 8.","DOI":"10.3390\/antiox8070213"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Jasinski, M., and Olszewska-Slonina, D. (2022). Serum paraoxonase-1 activity and the risk of prostate cancer recurrence in patients treated with radiotherapy. Antioxidants, 11.","DOI":"10.3390\/antiox11020346"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/12\/2394\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:32:44Z","timestamp":1760146364000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/12\/2394"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,2]]},"references-count":63,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["antiox11122394"],"URL":"https:\/\/doi.org\/10.3390\/antiox11122394","relation":{},"ISSN":["2076-3921"],"issn-type":[{"type":"electronic","value":"2076-3921"}],"subject":[],"published":{"date-parts":[[2022,12,2]]}}}