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.
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.
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.
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.
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.
Crowther, J. The ELISA Guidebook Series Editor; 2009; Vol. 516; ISBN 9781603272537.
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.
Hanahan, D.; Weinberg, R.A. Hallmarks of Cancer: The next Generation. Cell 2011, 144, 646–674, doi: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.
Blaustein, M.P.; Lederer, W.J.; Annunziato, L. Sodium / Calcium Exchange : Its Physiological Implications. Society 2008, 79, 763–854.
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.
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.
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.
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.
Nicholson, D.W.; Thornberry, N.A. Caspases: Killer Proteases. Trends Biochem. Sci. 1997, 22, 299–306, doi: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.
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.
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.
Ho, E. Zinc Deficiency, DNA Damage and Cancer Risk. J. Nutr. Biochem. 2004, 15, 572–578, doi: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.
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.
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