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| Antioxidant status in patients with bladder cancer regarding cancer stage and grade |
Zahid Leparaa,Jasmin Alića,*( ),Orhan Leparab,Hajrudin Spahovića,Almir Fajkićc
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aUrology Clinic, Clinical Center University of Sarajevo, Bolnička 25, 71 000 Sarajevo, Bosnia and Herzegovina
bDepartment of Physiology, Faculty of Medicine, University of Sarajevo, Čekaluša 90, 71 000 Sarajevo, Bosnia and Herzegovina
cDepartment of Pathophysiology, Faculty of Medicine, University of Sarajevo, Čekaluša 90, 71 000 Sarajevo, Bosnia and Herzegovina |
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Abstract Objective: The imbalance of antioxidants and pro-oxidants plays a crucial role in the carcinogenesis of bladder cancer (BC). This study aimed to evaluate serum antioxidant status in patients with BC and determine its potential use in the diagnosis and progression potential considerations following histopathological assessment.
Methods: A cross-sectional study included 90 patients with BC, divided into Ta, T1, and T2-T4 stage subgroups, and according to cancer progression potential, into low-grade (LG) and high-grade (HG) subgroups. The control group (CG) included 30 healthy volunteers. Antioxidant status was determined using the spectrophotometric method and standard laboratory tests.
Results: Serum superoxide dismutase activity was significantly higher in BC patients regarding cancer stage in comparison to the CG (p<0.001). Catalase activity was highest in T2-T4 subgroup and was significantly higher compared to the Ta (p<0.01) and T1 (p<0.05) subgroups. Serum albumin level was significantly lower in the BC group compared to the CG (p<0.001). In addition, it was significantly lower in T2-T4 subgroup compared to T1 and Ta subgroups (p<0.01). A significant negative correlation was found between tumor size and serum albumin level only (r=−0.386, p<0.01). Catalase activity was higher in HG subgroup (p=0.009), while bilirubin level was higher in LG subgroup (p=0.035). The optimal cut-off value of catalase activity in differentiating patients with LG and HG BC subgroups was ≥11.96 IU/L, and the specificity and sensitivity were 51.1% and 82.2%, respectively. Bilirubin level, for a calculated optimal cut-off value of ≥11.95 μmol/L, had a specificity of 44.1% and sensitivity of 80.0%.
Conclusion: More invasive stages of BC with greater progression potential are associated with an increase in enzymatic antioxidant activity and a decrease in non-enzymatic antioxidant capacity. It may suggest a possible role of antioxidants in the prediction and monitoring of illness trajectory.
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Received: 08 October 2020
Available online: 20 April 2023
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Corresponding Authors:
Jasmin Alić
E-mail: jasmin.allic@gmail.com
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| Variable | CG (n=30) | BC group (n=90) | p-Value | | Male/female, n (%) | 16 (53.3)/14 (46.7) | 65 (72.2)/25 (27.8) | NS | | Age, mean±SD, year | 66.86±3.67 | 68.12±2.89 | NS | | Smoking, n (%) | 13 (43.3) | 72 (80.0) | <0.001 | | Tumor size, median (IQR), cm | - | 2.0 (0.5-4.0) | - |
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Baseline characteristics of patients in CG and BC group.
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| Variable | CG (n=30) | BC group (n=90) | p-Value | | SOD activity, IU/mL | 32.62 (23.32-38.27) | 50.28 (39.81-58.04) | <0.001 | | Catalase activity, IU/L | 82.97 (0-261.76) | 85.23 (0.0-178.72) | NS | | Uric acid level, μmol/L | 290.50 (229.25-378.00) | 303.5 (236.25-370.75) | NS | | Albumin level, g/L | 41.00 (39.00-43.00) | 38.00 (34.00-40.00) | <0.001 | | Bilirubin level, μmol/L | 9.00 (7.00-12.22) | 9.5 (6.55-12.37) | NS |
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Comparative analyses of antioxidants in CG and BC group.
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| Variable | CG (n=30) | Ta subgroup (n=30) | T1 subgroup (n=30) | T2-T4 subgroup (n=30) | | SOD activity, IU/mL | 32.62 (23.32-38.27) | 52.10 (39.71-59.44)a | 51.16 (39.89-60.43)a | 48.29 (36.51-54.46)a | | Catalase activity, UI/L | 82.97 (0-26.76) | 45.97 (0-139.36) | 37.35 (0.0-178.72) | 154.38 (62.36-233.71)b,c | | Uric acid level, μmol/L | 290.50 (229.25-378.0) | 307.50 (235.50-370.50) | 297.00 (233.50-369.25) | 327.00 (249.50-444.0) | | Albumin level, g/L | 41.00 (39.00-43.00) | 38.50 (35.00-40.0)d | 39.00 (36.87-41.00)a | 33.50 (28.75-40.00)b,d,e | | Bilirubin level, μmol/L | 9.00 (7.00-12.22) | 11.55 (7.32-14.02) | 9.20 (6.92-12.07) | 8.45 (4.90-10.97)f |
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Comparative characteristics of patients in CG and bladder cancer subgroups.
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| Variables | LG (n=46) | HG (n=44) | p-Value | | SOD activitya, IU/mL | 49.79±16.16 | 46.08±13.66 | NS | | Catalase activityb, IU/L | 8.77 (0-139.00) | 138.00 (22.20-212.89) | 0.009 | | Uric acid levela, μmol/L | 303.86±92.45 | 337.17±126.31 | NS | | Albumin levelb, g/L | 39.0 (36.0-40.0) | 37.0 (30.0-40.5) | NS | | Bilirubin levelb, μmol/L | 10.20 (7.10-13.20) | 8.90 (5.50-11.25) | 0.035 |
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Comparative analysis of antioxidants in LG and HG bladder cancer subgroups.
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| Variable | Optimal cut-off value | AUC score, median (95% CI) | Sensitivity (%) | Specificity (%) | PPV (%) | NPV (%) | p-Value | | Catalase activity | ≥11.96 IU/L | 0.656 (0.546-0.775) | 82.2 | 51.1 | 62.7 | 74.1 | 0.009 | | Bilirubin level | ≥11.95 μmol/L | 0.630 (0.513-0.747) | 80.0 | 44.1 | 60.0 | 67.8 | 0.035 |
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Optimal cut-off, AUC with 95% CI, sensitivity, specificity, PPV, and NPV of serum catalase activity and bilirubin level in differentiating between patients with LG and HG bladder cancer.
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| [1] |
Sloan FA, Yashkin AP, Akushevich I, Inman BA. The cost to Medicare of bladder cancer care. Eur Urol Oncol 2020; 3: 515-22.
doi: S2588-9311(19)30016-1
pmid: 31412015
|
| [2] |
Freedman ND, Silverman DT, Hollenbeck AR, Schatzkin A, Abnet CC. Association between smoking and risk of bladder cancer among men and women. JAMA 2011; 306:737-45.
doi: 10.1001/jama.2011.1142
pmid: 21846855
|
| [3] |
Babjuk M, Burger M, Compérat EM, Gontero P, Mostafid AH, Palou J, et al. European Association of Urology guidelines on non-muscle-invasive bladder cancer (TaT1 and carcinoma in situ) d2019 update. Eur Urol 2019; 76:639-57.
doi: S0302-2838(19)30660-8
pmid: 31443960
|
| [4] |
Pisoschi AM, Pop A. The role of antioxidants in the chemistry of oxidative stress: a review. Eur J Med Chem 2015; 97:55-74.
doi: 10.1016/j.ejmech.2015.04.040
pmid: 25942353
|
| [5] |
Arikan S, Akcay T, Konukoglu D, Obek C, Kural AR. The relationship between antioxidant enzymes and bladder cancer. Neoplasma 2005; 52:314-7.
pmid: 16059648
|
| [6] |
Sawicka E, Kratz EM, Szymańska B, Gusik A, Wesolowski A, Kowal P, et al. Preliminary study on selected markers of oxidative stress, inflammation and angiogenesis in patients with bladder cancer. Pathol Oncol Res 2020; 26:821-31.
doi: 10.1007/s12253-019-00620-5
pmid: 30828780
|
| [7] |
Ha XF, Melendez JA, Mian BM. Oxidative stress index correlates with tumorigenic potential in bladder cancer cell lines. Cancer Res 2004; 64:397. https://aacrjournals.org/cancerres/article/64/7_Supplement/397/513165/Oxidative-stress-index-correlates-with-tumorigenic.
|
| [8] |
Savic-Radojevic A, Mimic-Oka J, Pljesa-Ercegovac M, Opacic M, Dragicevic D, Kravic T, et al. Glutathione S-trans-ferase-P1 expression correlates with increased antioxidant capacity in transitional cell carcinoma of the urinary bladder. Eur Urol 2007; 52:470-7.
doi: 10.1016/j.eururo.2007.01.046
pmid: 17267100
|
| [9] |
Ga?ecka E, Jacewicz R, Mrowicka M, Florkowski A, Ga?ecki P. [Antioxidative enzymesdstructure, properties, functions]. Pol Merkur Lek 2008; 25:266-8. [Article in Polish].
|
| [10] |
Miao L, St Clair DK. Regulation of superoxide dismutase genes: implications in disease. Free Radic Biol Med 2009; 15:344-56.
|
| [11] |
Fitzpatrick B, Schuler C, Leggett RE, Levin RM. Calcium effects on superoxide dismutase and catalase of the rabbit urinary bladder muscle and mucosa. Urol Int 2012; 88:107-11.
doi: 10.1159/000333144
pmid: 22094966
|
| [12] |
Jeon SH, Park JH, Chang SG. Expression of antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase) in human bladder cancer. Korean J Urol 2007; 48:921-6.
doi: 10.4111/kju.2007.48.9.921
|
| [13] |
Hempel N, Ye H, Abessi B, Mian B, Melendez JA. Altered redox status accompanies progression to metastatic human bladder cancer. Free Radic Biol Med 2009; 46:42-50.
doi: 10.1016/j.freeradbiomed.2008.09.020
|
| [14] |
Bayraktar N, Kilic S, Bayraktar MR, Aksoy N. Lipid peroxidation and antioxidant enzyme activities in cancerous bladder tissue and their relation with bacterial infection: a controlled clinical study. J Clin Lab Anal 2010; 24:25-30.
doi: 10.1002/jcla.20356
pmid: 20087949
|
| [15] |
Pirin??i N, Ge?it I, Güne? M, Yüksel MB, Kaba M, Tan?k S, et al. Serum adenosine deaminase, catalase and carbonic anhydrase activities in patients with bladder cancer. Clinics 2012; 67: 1443-6.
doi: 10.6061/clinics/2012(12)15
|
| [16] |
Cobanoglu U, Demir H, Duran M, ?ehitogullari A, Mergan D, Demir C. Erythrocyte catalase and carbonic anhydrase activities in lung cancer. Asian Pac J Cancer Prev APJCP 2010; 11: 1377-82.
|
| [17] |
Korotkina RN, Matskevich GN, Devlikanova ASh, Vishnevskii AA, Kunitsyn AG, Karelin AA. Activity of glutathione-metabolizing and antioxidant enzymes in malignant and benign tumors of human lungs. Bull Exp Biol Med 2002; 133:606-8.
doi: 10.1023/A:1020206514239
|
| [18] |
Zainal IG, AL-Dori M, Abdul ANM. Study of some antioxidants in plasma of patients with bladder cancer. Eng Technol J 2009; 27:751-8.
|
| [19] |
Ma Q. Advances in mechanisms of anti-oxidation. Discov Med 2014; 17:121-30.
pmid: 24641954
|
| [20] |
?olak E, Dimitrijevi?-Sre?kovi? V, Djordjevi? PB, Stankovi? S, Gli?i? B, Sre?kovi? B, et al. Biomarkers of enzymatic and non-enzymatic antioxidative defense in type 2 diabetes mellitusdcomparative analysis. Biochem Med 2008; 18: 42-51.
|
| [21] |
Todorovi? T, Do?i? I, Mandi? B, Marjanovi? M. [Antioksidativna uloga pljuva?ke u o?uvanju zdravlja usta]. Vojnosanit Pregl 2005; 62: 575-9.[Article in Serbian].
pmid: 16171022
|
| [22] |
Zhu HQ, Gao Y, Guo HR, Kong QZ, Ma Y, Wang JZ, et al. Pretreatment with bilirubin protects islet against oxidative injury during isolation and purification. Transplant Proc 2011; 43: 1810-4.
doi: 10.1016/j.transproceed.2010.12.058
|
| [23] |
Keshavan P, Schwemberger SJ, Smith DL, Babcock GF, Zucker SD. Unconjugated bilirubin induces apoptosis in colon cancer cells by triggering mitochondrial depolarization. Int J Cancer 2004; 112:433-45.
pmid: 15382069
|
| [24] |
Chandran V, Anitha M, Avinash SS, Rao GM, Shetty BV, Sudha K. Protein oxidation: a potential cause of hypoalbuminemia in oral cancer. Resour Biomed Res Educ 2012; 23:227-30.
|
| [25] |
Al-Muhammadi MO, Mahmood EH, Abd BA. Some biochemical changes in patients with bladder cancer. Med J Babylon 2011; 8:412-7.
|
| [26] |
Bastide N, Dartois L, Dyevre V, Dossus L, Fagherazzi G, Serafini M, et al. Dietary antioxidant capacity and all-cause and cause-specific mortality in the E3N/EPIC cohort study. Eur J Nutr 2017; 56:1233-43.
doi: 10.1007/s00394-016-1172-6
pmid: 26887577
|
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| [2] |
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