CORRELATION BETWEEN TBARS VALUE IN SERUM AND TISSUE AS OXIDATIVE STRESS MARKERS IN PREMALIGNANT AND MALIGNANT CERVICAL LESIONS
Abstract
Introduction: Numerous risk factors affect the development of cervical intraepithelial neoplasia (CIN) and cervical cancer (CC), with high-risk subtypes of the human papillomavirus (HPV) being the most significant. Oxidative stress (OS) plays an important role in the pathogenesis of CC and CIN as a risk factor. A commonly used marker of OS, which measures lipid peroxidation products in cells, tissues, and body fluids, is thiobarbituric acid reactive substances (TBARS). This study aimed to determine the correlation between TBARS levels in tissue and serum and evaluate their diagnostic significance in patients with cervical lesions.
Patients and methods: The research was conducted at the Clinical Center of the University of Sarajevo. The experimental group consisted of 200 female patients with biopsy-confirmed changes consistent with CIN, carcinoma in situ (CIS), and CC. The control group (N=40) had biopsy-confirmed non-pathological findings. The concentration of TBARS was determined for all subjects from biopsy samples and serum according to standard laboratory practice.
Results: We found a significant difference in serum/tissue TBARS levels between study groups. Serum/tissue levels of TBARS in patients with CIS were significantly higher compared to the control group, patients with CIN 1, CIN 2, CIN 3, and patients with CC (p<0.05 for all). There was a significant positive correlation between TBARS levels in serum (µM) and TBARS levels in tissue (µM) (Pearson's r=0.494, p<0.001). Tissue and serum TBARS levels are major differentiation markers between CIS patients and the control group, as well as patients with CIN 1, CIN 2, CIN 3, and CC.
Conclusion: Patients with CIN and CC exhibit increased oxidative stress, indicated by higher levels of TBARS in their tissue and serum compared to healthy controls. TBARS levels in tissue are positively correlated with levels in serum. Tissue and serum TBARS levels are significant markers for differentiating the clinical stages of the disease.
References
Arbyn M, Weiderpass E, Bruni L, de Sanjosé S, Saraiya M, Ferlay J, et al. Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis. Lancet Glob Health. 2020;8(2):e191-e203. doi: 10.1016/S2214-109X(19)30482-6. Epub 2019 Dec 4. Erratum in: Lancet Glob Health. 2022;10(1):e41.
Lukac A, Sulovic N, Smiljic S, Ilic AN, Saban O. The prevalence of the most important risk factors associated with cervical cancer. Mater Sociomed. 2018;30(2):131-5. doi: 10.5455/msm.2018.30.131-135.
Wang Z, Wang J, Fan J, Zhao W, Yang X, Wu L, et al. Risk factors for cervical intraepithelial neoplasia and cervical cancer in Chinese women: large study in Jiexiu, Shanxi Province, China. J Cancer. 2017;8(6):924-32. doi: 10.7150/jca.17416.
Zahra K, Patel S, Dey T, Pandey U, Mishra SP. A study of oxidative stress in cervical cancer- an institutional study. Biochem Biophys Rep. 2020;25:100881. doi: 10.1016/j.bbrep.2020.100881.
Asotić A, Asotić Memić A, Memić M, Asotić K, Asotić A. Development of cervical intraepithelial neoplasia and invasive cervical cancer due to oxidative stress. Sanamed. 2024; 19(1): 39–44. doi: 10.5937/sanamed19-49657.
Chang HK, Seo SS, Myong JP, Yu YL, Byun SW. Incidence and costs of cervical intraepithelial neoplasia in the Korean population. J Gynecol Oncol. 2019;30(3):e37. doi: 10.3802/jgo.2019.30.e37.
Barrera G. Oxidative stress and lipid peroxidation products in cancer progression and therapy. ISRN Oncol. 2012;2012:137289. doi: 10.5402/2012/137289.
Klaunig JE, Kamendulis LM, Hocevar BA. Oxidative stress and oxidative damage in carcinogenesis. Toxicol Pathol. 2010;38(1):96-109. doi: 10.1177/0192623309356453.
Lepara Z, Lepara O, Fajkić A, Rebić D, Alić J, Spahović H. Serum malondialdehyde (MDA) level as a potential biomarker of cancer progression for patients with bladder cancer. Rom J Intern Med. 2020;58(3):146-52. doi: 10.2478/rjim-2020-0008.
Schuch AP, Moreno NC, Schuch NJ, Menck CFM, Garcia CCM. Sunlight damage to cellular DNA: Focus on oxidatively generated lesions. Free Radic Biol Med. 2017;107:110-24. doi: 10.1016/j.freeradbiomed.2017.01.029.
Thanan R, Oikawa S, Hiraku Y, Ohnishi S, Ma N, Pinlaor S, et al. Oxidative stress and its significant roles in neurodegenerative diseases and cancer. Int J Mol Sci. 2014;16(1):193-217. doi: 10.3390/ijms16010193.
Klaunig JE. Oxidative stress and cancer. Curr Pharm Des. 2018;24(40):4771-8. doi: 10.2174/1381612825666190215121712.
Calaf GM, Urzua U, Termini L, Aguayo F. Oxidative stress in female cancers. Oncotarget. 2018;9(34):23824-42. doi: 10.18632/oncotarget.25323.
Clemente SM, Martínez-Costa OH, Monsalve M, Samhan-Arias AK. Targeting Lipid Peroxidation for cancer treatment. Molecules. 2020;25(21):5144. doi: 10.3390/molecules25215144.
Banerjee S, Mukherjee S, Mitra S, Singhal P. Comparative evaluation of mitochondrial antioxidants in oral potentially malignant disorders. Kurume Med J. 2020;66(1):15-27. doi: 10.2739/kurumemedj.MS661009.
Jelić M, Mandić A, Kladar N, Sudji J, Božin B, Srdjenović B. Lipid peroxidation, antioxidative defense and level of 8-hydroxy-2-deoxyguanosine in cervical cancer patients. J Med Biochem. 2018;37(3):336-45. doi: 10.1515/jomb-2017-0053.
Zahra K, Patel S, Dey T, Pandey U, Mishra SP. A study of oxidative stress in cervical cancer- an institutional study. Biochem Biophys Rep. 2020;25:100881. doi: 10.1016/j.bbrep.2020.100881.
Naidu MS, Suryakar AN, Swami SC, Katkam RV, Kumbar KM. Oxidative stress and antioxidant status in cervical cancer patients. Indian J Clin Biochem. 2007;22(2):140-4. doi: 10.1007/BF02913333.
do Val Carneiro JL, Nixdorf SL, Mantovani MS, da Silva do Amaral Herrera AC, Aoki MN, Amarante MK, et al. Plasma malondialdehyde levels and CXCR4 expression in peripheral blood cells of breast cancer patients. J Cancer Res Clin Oncol. 2009;135(8):997-1004. doi: 10.1007/s00432-008-0535-7.
Jelic MD, Mandic AD, Maricic SM, Srdjenovic BU. Oxidative stress and its role in cancer. J Cancer Res Ther. 2021;17(1):22-8. doi: 10.4103/jcrt.JCRT_862_16.
Carneiro SR, da Silva Lima AA, de Fátima Silva Santos G, de Oliveira CSB, Almeida MCV, da Conceição Nascimento Pinheiro M. Relationship between oxidative stress and physical activity in women with squamous intraepithelial lesions in a cervical cancer control program in the Brazilian Amazon. Oxid Med Cell Longev. 2019;2019:8909852. doi: 10.1155/2019/8909852.
Visalli G, Riso R, Facciolà A, Mondello P, Caruso C, Picerno I, et al. Higher levels of oxidative DNA damage in cervical cells are correlated with the grade of dysplasia and HPV infection. J Med Virol. 2016;88(2):336-44. doi: 10.1002/jmv.24327.
Gonçalves TL, Erthal F, Corte CL, Müller LG, Piovezan CM, Nogueira CW, et al. Involvement of oxidative stress in the pre-malignant and malignant states of cervical cancer in women. Clin Biochem. 2005;38(12):1071-5. doi: 10.1016/j.clinbiochem.2005.09.008.
Manju V, Kalaivani Sailaja J, Nalini N. Circulating lipid peroxidation and antioxidant status in cervical cancer patients: a case-control study. Clin Biochem. 2002;35(8):621-5. doi: 10.1016/s0009-9120(02)00376-4.
Shah S, Kalal BS. Oxidative stress in cervical cancer and its response to chemoradiation. Turk J Obstet Gynecol. 2019;16(2):124-8. doi: 10.4274/tjod.galenos.2019.19577.
Borges BES, Brito EB, Fuzii HT, Baltazar CS, Sá AB, Silva CIMD, et al. Human papillomavirus infection and cervical cancer precursor lesions in women living by Amazon rivers: investigation of relations with markers of oxidative stress. Einstein (Sao Paulo). 2018;16(3):eAO4190. doi: 10.1590/s1679-45082018ao4190.
Asotic A. The role of oxidative stress in the development of cervical intraepithelial neoplasia and invasive cervical cancer [PhD Dissertation]. [Banja Luka]: Faculty of Medicine, University of Banja Luka;2022.105 p. Available from https://fedora.unibl.org/fedora/get/o:2463/bdef:Content/get
Copyright (c) 2024 Sanamed
This work is licensed under a Creative Commons Attribution 4.0 International License.
Journal Sanamed is published under an Open Access license. All its content is available free of charge. Users can read, download, copy, distribute, print, search the full text of articles, as well as establish HTML links to them, without having to seek the consent of the author or publisher.
The right to use content without consent does not release the users from the obligation to give the credit to the journal and its content in a manner described under CC BY.