Clinical Significance of Apoptosis Marker Caspase-3, Tumor Marker CEA, and Electrolyte Imbalance in Breast Cancer Patients Casp3-CEA in BC
Abstract
Background: Reliable circulating biomarkers remain clinically important in the evaluation of breast cancer. This cross-sectional study assessed serum caspase-3, carcinoembryonic antigen (CEA), and certain electrolyte parameters in a control group of healthy individuals and breast cancer patients at different clinical stages.
Methods: Ninety female participants were divided into Control (n=30), Newly Diagnosed (G1, n=20), and Treated (G2, n=40) groups. Serum Caspase-3, CEA, and electrolytes (Zn2+, Ca2+, Na+, K+) were measured. Blood samples in the treated group were collected after completion of the fourth chemotherapy cycle during routine follow-up visits. No participants were excluded after laboratory analysis due to missing biomarker data. Data were analyzed using ANOVA and ROC curves. A p-value < 0.05 was considered statistically significant.
Results: Caspase-3 levels were lowest in the newly diagnosed group (G1), whereas treated patients (G2) showed higher values than G1. One-way ANOVA demonstrated a statistically significant difference among the study groups for Caspase-3 (p = 0.004). CEA concentrations also differed significantly between groups (p = 0.002). Significant differences were observed for Zn²⁺ (p < 0.001), Ca²⁺ (p < 0.0001), Na⁺ (p < 0.001), and K⁺ (p < 0.0001). ROC analysis indicated moderate diagnostic performance for CEA (AUC = 0.7537).
Conclusion: Between-group differences were observed in serum Caspase-3, CEA, and selected electrolyte levels.
References
Harris, J.R.; Lippman, M.E.; Morrow, M.; Osborne, C.K. Diseases of the Breast, 5e; Lippincott Williams & Wilkins, 2014; ISBN 978-1-4511-8627-7.
McIlwain, D.R.; Berger, T.; Mak, T.W. Caspase Functions in Cell Death and Disease. Cold Spring Harb. Perspect. Biol. 2015, 7, doi:10.1101/cshperspect.a026716. DOI: https://doi.org/10.1101/cshperspect.a026716
Sturgeon, C.M.; Duffy, M.J.; Stenman, U.H.; Lilja, H.; Brünner, N.; Chan, D.W.; Babaian, R.; Bast, R.C.; Dowell, B.; Esteva, F.J.; et al. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for Use of Tumor Markers in Testicular, Prostate, Colorectal, Breast, and Ovarian Cancers. Clin. Chem. 2008, 54, doi:10.1373/clinchem.2008.105601. DOI: https://doi.org/10.1373/clinchem.2008.105601
Wagle, D.B.D.; Deshmukh, D.A.V.; Mangam, D.S.N.; Gangane, D.N.M. Can Caspase-3 Act as a Potential Prognostic Biomarker in Breast Cancer? - A Retrospective Pilot Study in Central India. Int. J. Clin. Diagnostic Pathol. 2023, 6, 76–83, doi:10.33545/pathol.2023.v6.i2b.520. DOI: https://doi.org/10.33545/pathol.2023.v6.i2b.520
Duque, G.; Manterola, C.; Otzen, T.; Arias, C.; Palacios, D.; Mora, M.; Galindo, B.; Holguín, J.P.; Albarracín, L. Cancer Biomarkers in Liquid Biopsy for Early Detection of Breast Cancer: A Systematic Review. Clin. Med. Insights Oncol. 2022, 16, doi:10.1177/11795549221134831. DOI: https://doi.org/10.1177/11795549221134831
Rosner, M.H.; Dalkin, A.C. Electrolyte Disorders Associated With Cancer. Adv. Chronic Kidney Dis. 2014, 21, 7–17, doi:10.1053/j.ackd.2013.05.005. DOI: https://doi.org/10.1053/j.ackd.2013.05.005
Crowther, J. The ELISA Guidebook Series Editor; 2009; Vol. 516; ISBN 9781603272537. DOI: https://doi.org/10.1007/978-1-60327-254-4
Tietz N.W. Tietz NW. Clinical Guide to Laboratory Tests. 4th Ed. Saunders; ALAN H.B., Ed.; Publishing Director: Andrew Allen Executive Editor: Loren Wilson Developmental Editor: Ellen Wurm Publishing Services Manager: Pat Joiner Project Manager: David Stein Senior Designer: Andrea Lutes, 2006; ISBN 9780721679754.
Elmore, S. Apoptosis: A Review of Programmed Cell Death. Toxicol. Pathol. 2007, 35, 495–516, doi:10.1080/01926230701320337. DOI: https://doi.org/10.1080/01926230701320337
Hanahan, D.; Weinberg, R.A. Hallmarks of Cancer: The next Generation. Cell 2011, 144, 646–674, doi:10.1016/j.cell.2011.02.013. DOI: https://doi.org/10.1016/j.cell.2011.02.013
Duffy, M.J. Serum Tumor Markers in Breast Cancer: Are They of Clinical Value? Clin. Chem. 2006, 52, 345–351, doi:10.1373/clinchem.2005.059832. DOI: https://doi.org/10.1373/clinchem.2005.059832
Blaustein, M.P.; Lederer, W.J.; Annunziato, L. Sodium / Calcium Exchange : Its Physiological Implications. Society 2008, 79, 763–854. DOI: https://doi.org/10.1152/physrev.1999.79.3.763
Prasad, A.S. Zinc in Human Health: Effect of Zinc on Immune Cells. Mol. Med. 2008, 14, 353–357, doi:10.2119/2008-00033.Prasad. DOI: https://doi.org/10.2119/2008-00033.Prasad
Orrenius, S.; Zhivotovsky, B.; Nicotera, P. Regulation of Cell Death: The Calcium-Apoptosis Link. Nat. Rev. Mol. Cell Biol. 2003, 4, 552–565, doi:10.1038/nrm1150. DOI: https://doi.org/10.1038/nrm1150
Zweig, M.H.; Campbell, G. Receiver-Operating Characteristic (ROC) Plots: A Fundamental Evaluation Tool in Clinical Medicine. Clin. Chem. 1993, 39, 561–577, doi:10.1093/clinchem/39.4.561. DOI: https://doi.org/10.1093/clinchem/39.4.561
Gogtay, N.J.; Thatte, U.M. Statistical Evaluation of Diagnostic Tests – Part 2 [Pre-Test and Post-Test Probability and Odds, Likelihood Ratios, Receiver Operating Characteristic Curve, Youden’s Index and Diagnostic Test Biases]. J. Assoc. Physicians India 2017, 65, 86–91.
Vidak, E.; Vizovišek, M.; Kavčič, N.; Biasizzo, M.; Fonović, M.; Turk, B. Apoptotic Caspases-3 and -7 Cleave Extracellular Domains of Membrane-Bound Proteins from MDA-MB-231 Breast Cancer Cells. Int. J. Mol. Sci. 2025, 26, doi:10.3390/ijms26083466. DOI: https://doi.org/10.3390/ijms26083466
Nicholson, D.W.; Thornberry, N.A. Caspases: Killer Proteases. Trends Biochem. Sci. 1997, 22, 299–306, doi:10.1016/S0968-0004(97)01085-2. DOI: https://doi.org/10.1016/S0968-0004(97)01085-2
Pistritto, G.; Trisciuoglio, D.; Ceci, C.; Alessia Garufi; D’Orazi, G. Apoptosis as Anticancer Mechanism: Function and Dysfunction of Its Modulators and Targeted Therapeutic Strategies. Aging (Albany. NY). 2016, 8, 603–619, doi:10.18632/aging.100934. DOI: https://doi.org/10.18632/aging.100934
Wong, R.S.Y. Apoptosis in Cancer: From Pathogenesis to Treatment. J. Exp. Clin. Cancer Res. 2011, 30, 1–14, doi:10.1186/1756-9966-30-87. DOI: https://doi.org/10.1186/1756-9966-30-87
Park, B.W.; Oh, J.W.; Kim, J.H.; Park, S.H.; Kim, K.S.; Kim, J.H.; Lee, K.S. Preoperative CA 15-3 and CEA Serum Levels as Predictor for Breast Cancer Outcomes. Ann. Oncol. 2008, 19, 675–681, doi:10.1093/annonc/mdm538. DOI: https://doi.org/10.1093/annonc/mdm538
Ho, E. Zinc Deficiency, DNA Damage and Cancer Risk. J. Nutr. Biochem. 2004, 15, 572–578, doi:10.1016/j.jnutbio.2004.07.005. DOI: https://doi.org/10.1016/j.jnutbio.2004.07.005
Prasad, A.S. Discovery of Human Zinc Deficiency: Its Impact on Human Health and Disease. Adv. Nutr. 2013, 4, 176–190, doi:10.3945/an.112.003210. DOI: https://doi.org/10.3945/an.112.003210
Valko, M.; Rhodes, C.J.; Moncol, J.; Izakovic, M.; Mazur, M. Free Radicals, Metals and Antioxidants in Oxidative Stress-Induced Cancer. Chem. Biol. Interact. 2006, 160, 1–40, doi:10.1016/j.cbi.2005.12.009. DOI: https://doi.org/10.1016/j.cbi.2005.12.009
Authors
Copyright (c) 2026 Archives of Breast Cancer
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Copyright©. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International License, which permits copy and redistribution of the material in any medium or format or adapt, remix, transform, and build upon the material for any purpose, except for commercial purposes.