Association of potent inflammatory Cytokine and Oxidative DNA Damage Biomarkers in Stomach cancer patients

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Akam Jasim Mustafa
Parween Abdulsamad Ismail

Abstract

The infection with H. Pylori stimulates a signaling cascade that causes the generation of Cytokines and provokes Oxidative stress that is involved in the chronic inflammatory response leads to Gastric cancers. Reactive oxygen species (ROS) produce 8-Hydroxydeoxyguanosine (8-OHdG), the persistent oxidative DNA damage product. The study objective was to assess if there was a link between inflammatory cytokine levels and the presence of Oxidative DNA damage in Gastric tumor patients. In addition, evaluation of the diagnostic and prognostic value of Oxidative DNA damage and inflammatory cytokine biomarkers for Stomach cancers is being conducted. The study was accomplished on medically diagnosed Stomach cancer patients before any form of treatment. A total of 33 patients with Gastric cancers were selected and divided into Stages I, II, and III according to clinical pathology, and 32 age-matched healthy subjects as a control group. The Serum 8-OHdG, IL-6, TNF-α, IFN-γ & CEA were evaluated. The results revealed a highly significant rise (P<0.0001) in blood levels of 8-OHdG, TNF-α, & IFN-γ, and a non-significant (P=0.4747) increasing in IL-6 in GC patients compared to Controls, with levels gradually increasing as disease stages progressed. Furthermore, in GC patients, there was an insignificant (P=0.3472) positive correlation (r=0.1292) among 8-OHdG, IL-6, and CEA levels, but a noteworthy (P<0.0001) positive correlation (r=0.7235) among 8-OHdG, TNF-α, and CEA levels. In GC patients, however, there was an insignificant (P=0.6342) negative correlation (r=-0.06559) among 8-OHdG, IFN-γ, and CEA levels. The results of the current study show a strong link between serum levels of the 8-OHdG as well as inflammatory cytokines in GC patients. The significant enhancement in oxidative DNA damage, as well as overexpression of inflammatory cytokine biomarkers and CEA in the blood suggests that Oxidative stress and chronic inflammation are included in GC carcinogenesis. These observations suggest that 8-OHdG, TNF-α, & IFN-γ are viable biomarkers for the Gastric tumor prediction.

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Mustafa AJ, Ismail PA. Association of potent inflammatory Cytokine and Oxidative DNA Damage Biomarkers in Stomach cancer patients. Baghdad Sci.J [Internet]. [cited 2022Jun.26];:1313. Available from: https://bsj.uobaghdad.edu.iq/index.php/BSJ/article/view/6589
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References

Galadari S, Rahman A, Pallichankandy S, Thayyullathil F. Reactive oxygen species and cancer paradox: To promote or to suppress? Free Radic Biol Med. 2017;104:144-64.

Basu AK. DNA Damage, Mutagenesis and Cancer. Int J Mol Sci. 2018;19(4):970.

Klaunig JE. Oxidative Stress and Cancer. Curr Pharm Des. 2018;24(40):4771-78.

Whitaker AM, Schaich MA, Smith MR, Flynn TS, Freudenthal BD. Base excision repair of oxidative DNA damage: from mechanism to disease. Front Biosci (Landmark Ed). 2017;22:1493-522.

Al-Taie A, Sancar M, Izzettin FV. Chapter 17 - 8-Hydroxydeoxyguanosine: A valuable predictor of oxidative DNA damage in cancer and diabetes mellitus. In: Preedy VR, Patel VB, editors. Cancer (Second Edition). San Diego: Academic Press; 2021. p. 179-87.

Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Pineros M, et al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer. 2019;144(8):1941-53.

Park JY, Forman D, Waskito LA, Yamaoka Y, Crabtree JE. Epidemiology of Helicobacter pylori and CagA-Positive Infections and Global Variations in Gastric Cancer. Toxins. 2018;10(4):163.

Chmiela M, Karwowska Z, Gonciarz W, Allushi B, Stączek P. Host pathogen interactions in Helicobacter pylori related gastric cancer. World J Gastroenterol. 2017;23(9):1521-40.

Díaz P, Valenzuela Valderrama M, Bravo J, Quest AF. Helicobacter pylori and gastric cancer: adaptive cellular mechanisms involved in disease progression. Front Microbiol. 2018;9:5.

Khadem-Ansari M-H, Nozari S, Asoudeh M, Rasmi Y, Faridvand Y. Elevated serum 8-hydroxy-2’-deoxyguanosine, nitrite, and nitrate in patients with stage I multiple myeloma. Int J Cancer Manag. 2017;10(10).

Karki K, Pande D, Negi R, Khanna RS, Khanna HD. An Assessment of Oxidative Damage and Non-Enzymatic Antioxidants Status Alteration in Relation to Disease Progression in Breast Diseases. Med Sci (Basel). 2016;4(4):17.

Borrego S, Vazquez A, Dasí F, Cerdá C, Iradi A, Tormos C, et al. Oxidative stress and DNA damage in human gastric carcinoma: 8-Oxo-7'8-dihydro-2'-deoxyguanosine (8-oxo-dG) as a possible tumor marker. Int J Mol Sci. 2013;14(2):3467-86.

Mazlumoglu MR, Ozkan O, Alp HH, Ozyildirim E, Bingol F, Yoruk O, et al. Measuring oxidative DNA damage with 8-hydroxy-2’-deoxyguanosine levels in patients with laryngeal cancer. Ann Otol Rhinol Laryngol. 2017;126(2):103-09.

Guo C, Li X, Wang R, Yu J, Ye M, Mao L, et al. Association between oxidative DNA damage and risk of colorectal cancer: sensitive determination of urinary 8-hydroxy-2′-deoxyguanosine by UPLC-MS/MS analysis. Sci Rep. 2016;6(1):1-9.

Qing X, Shi D, Lv X, Wang B, Chen S, Shao Z. Prognostic significance of 8-hydroxy-2'-deoxyguanosine in solid tumors: a meta-analysis. BMC Cancer. 2019;19(1):997.

Butcher LD, den Hartog G, Ernst PB, Crowe SE. Oxidative Stress Resulting From Helicobacter pylori Infection Contributes to Gastric Carcinogenesis. Cell Mol Gastroenterol Hepatol. 2017;3(3):316-22.

Kawanishi S, Ohnishi S, Ma N, Hiraku Y, Murata M. Crosstalk between DNA damage and inflammation in the multiple steps of carcinogenesis. Int J Mol Sci. 2017;18(8):1808.

Fu L, Xie C. A lucid review of Helicobacter pylori-induced DNA damage in gastric cancer. Helicobacter. 2019;24(5):e12631.

Gönenç A, Hacışevki A, Aslan S, Torun M, Şimşek B. Increased oxidative DNA damage and impaired antioxidant defense system in patients with gastrointestinal cancer. Eur J Intern Med. 2012;23(4):350-54.

Diakowska D, Lewandowski A, Kopec W, Diakowski W, Chrzanowska T. Oxidative DNA damage and total antioxidant status in serum of patients with esophageal squamous cell carcinoma. Hepatogastroenterology. 2007;54(78):1701-4.

Kubo N, Morita M, Nakashima Y, Kitao H, Egashira A, Saeki H, et al. Oxidative DNA damage in human esophageal cancer: clinicopathological analysis of 8-hydroxydeoxyguanosine and its repair enzyme. Dis Esophagus. 2014;27(3):285-93.

Crohns M, Saarelainen S, Erhola M, Alho H, Kellokumpu-Lehtinen P. Impact of radiotherapy and chemotherapy on biomarkers of oxidative DNA damage in lung cancer patients. Clin Biochem. 2009;42(10-11):1082-90.

Cao C, Lai T, Li M, Zhou H, Lv D, Deng Z, et al. Smoking-promoted oxidative DNA damage response is highly correlated to lung carcinogenesis. Oncotarget. 2016;7(14):18919.

Wei YC, Zhou FL, He DL, Bai JR, Hui LY, Wang XY, et al. The level of oxidative stress and the expression of genes involved in DNA-damage signaling pathways in depressive patients with colorectal carcinoma. J Psychosom Res. 2009;66(3):259-66.

Cobanoglu U, Demir H, Cebi A, Sayir F, Alp HH, Akan Z, et al. Lipid peroxidation, DNA damage and coenzyme Q10 in lung cancer patients--markers for risk assessment? Asian Pac J Cancer Prev. 2011;12(6):1399-403.

Erturk K, Tastekin D, Serilmez M, Bilgin E, Bozbey HU, Vatansever S. Clinical significance of serum interleukin-29, interleukin-32, and tumor necrosis factor alpha levels in patients with gastric cancer. Tumour Biol. 2016;37(1):405-12.

Xu T, Kong Z, Zhao H. Relationship between tumor necrosis factor-α rs361525 polymorphism and gastric cancer risk: A meta-analysis. Front physiol. 2018;9:469.

Zheng W, Zhang S, Zhang S, Min L, Wang Y, Xie J, et al. The relationship between tumor necrosis factor-alpha polymorphisms and gastric cancer risk: An updated meta-analysis. Biomed Rep. 2017;7(2):133-42.

Yan Y, Yu Z, Lu J, Jin P, Tang Z, Hu Y. Predictive values profiling of interleukin-2, interleukin-8, tumor necrosis factor-alpha, procalcitonin, and C-reactive protein in critical gastrointestinal cancer patients. J Gastrointest Oncol. 2021;12(4):1398-406.

Jain SS, Bird RP. Elevated expression of tumor necrosis factor-alpha signaling molecules in colonic tumors of Zucker obese (fa/fa) rats. Int J Cancer. 2010;127(9):2042-50.

Gambhir S, Vyas D, Hollis M, Aekka A, Vyas A. Nuclear factor kappa B role in inflammation associated gastrointestinal malignancies. World J Gastroenterol. 2015;21(11):3174-83.

Cruceriu D, Baldasici O, Balacescu O, Berindan-Neagoe I. The dual role of tumor necrosis factor-alpha (TNF-alpha) in breast cancer: molecular insights and therapeutic approaches. Cell Oncol (Dordr). 2020;43(1):1-18.

Mahdavi Sharif P, Jabbari P, Razi S, Keshavarz-Fathi M, Rezaei N. Importance of TNF-alpha and its alterations in the development of cancers. Cytokine. 2020;130:155066.

Deryugina EI, Soroceanu L, Strongin AY. Up-regulation of vascular endothelial growth factor by membrane-type 1 matrix metalloproteinase stimulates human glioma xenograft growth and angiogenesis. Cancer Res. 2002;62(2):580-8.

Chuang MJ, Sun KH, Tang SJ, Deng MW, Wu YH, Sung JS, et al. Tumor-derived tumor necrosis factor-alpha promotes progression and epithelial-mesenchymal transition in renal cell carcinoma cells. Cancer Sci. 2008;99(5):905-13.

Wang X, Lin Y. Tumor necrosis factor and cancer, buddies or foes? Acta Pharmacol Sin. 2008;29(11):1275-88.

Zhao C, Lu X, Bu X, Zhang N, Wang W. Involvement of tumor necrosis factor-alpha in the upregulation of CXCR4 expression in gastric cancer induced by Helicobacter pylori. BMC Cancer. 2010;10(1):419.

Senthilkumar C, Niranjali S, Jayanthi V, Ramesh T, Devaraj H. Molecular and histological evaluation of tumor necrosis factor-alpha expression in Helicobacter pylori-mediated gastric carcinogenesis. J Cancer Res Clin Oncol. 2011;137(4):577-83.

Bounder G, Jouimyi MR, Boura H, Jouhadi H, Badre W, Benomar H, et al. Association of Tumor Necrosis Factor Receptor 1 Promoter Gene Polymorphisms (-580 A/G and-609 G/T) and TNFR1 Serum Levels with the Susceptibility to Gastric Precancerous Lesions and Gastric Cancer Related to H. pylori Infection in a Moroccan Population. Biomed Res Int. 2020;1(2451854):1-7.

Lee J, Park KH, Ryu JH, Bae HJ, Choi A, Lee H, et al. Natural killer cell activity for IFN-gamma production as a supportive diagnostic marker for gastric cancer. Oncotarget. 2017;8(41):70431.

Zhao H, Dong N, Liu T, Zhang P, Zheng Y, Yang L, et al. Clinical Significance of Serum Type III Interferons in Patients with Gastric Cancer. J Interferon Cytokine Res. 2019;39(3):155-63.

Abdollahi H, Shams S, Zahedi MJ, Darvish Moghadam S, Hayatbakhsh MM, Jafarzadeh A. IL-10, TNF-alpha and IFN-gamma levels in serum and stomach mucosa of Helicobacter pylori-infected patients. Iran J Allergy Asthma Immunol. 2011;10(4):267-71.

Lindgren A, Yun CH, Sjoling A, Berggren C, Sun JB, Jonsson E, et al. Impaired IFN-gamma production after stimulation with bacterial components by natural killer cells from gastric cancer patients. Exp Cell Res. 2011;317(6):849-58.

Sanchez-Zauco N, Torres J, Gomez A, Camorlinga-Ponce M, Munoz-Perez L, Herrera-Goepfert R, et al. Circulating blood levels of IL-6, IFN-gamma, and IL-10 as potential diagnostic biomarkers in gastric cancer: a controlled study. BMC Cancer. 2017;17(1):384.

Tu SP, Quante M, Bhagat G, Takaishi S, Cui G, Yang XD, et al. IFN-gamma inhibits gastric carcinogenesis by inducing epithelial cell autophagy and T-cell apoptosis. Cancer Res. 2011;71(12):4247-59.

Ito N, Tsujimoto H, Ueno H, Xie Q, Shinomiya N. Helicobacter pylori-Mediated Immunity and Signaling Transduction in Gastric Cancer. J Clin Med. 2020;9(11):3699.

Perfetto B, Buommino E, Canozo N, Paoletti I, Corrado F, Greco R, et al. Interferon-gamma cooperates with Helicobacter pylori to induce iNOS-related apoptosis in AGS gastric adenocarcinoma cells. Res Microbiol. 2004;155(4):259-66.

Szczepanik AM, Scislo L, Scully T, Walewska E, Siedlar M, Kolodziejczyk P, et al. IL-6 serum levels predict postoperative morbidity in gastric cancer patients. Gastric Cancer. 2011;14(3):266-73.

Madej-Michniewicz A, Budkowska M, Salata D, Dolegowska B, Starzynska T, Blogowski W. Evaluation of selected interleukins in patients with different gastric neoplasms: a preliminary report. Sci Rep. 2015;5(1):14382.

Yin Y, Si X, Gao Y, Gao L, Wang J. The nuclear factor-kappaB correlates with increased expression of interleukin-6 and promotes progression of gastric carcinoma. Oncol Rep. 2013;29(1):34-8.

Bockerstett KA, DiPaolo RJ. Regulation of Gastric Carcinogenesis by Inflammatory Cytokines. Cell Mol Gastroenterol Hepatol. 2017;4(1):47-53.

Zhang XY, Zhang PY, Aboul-Soud MA. From inflammation to gastric cancer: Role of Helicobacter pylori. Oncol Lett. 2017;13(2):543-48.

Rija FF, Hussein SZ, Abdalla MA. Physiological and Immunological Disturbance in Rheumatoid Arthritis Patients. Baghdad Sci J. 2021;18(2):0247-47.

Wang Z, Si X, Xu A, Meng X, Gao S, Qi Y, et al. Activation of STAT3 in human gastric cancer cells via interleukin (IL)-6-type cytokine signaling correlates with clinical implications. PLoS One. 2013;8(10):e75788.

Hara M, Nagasaki T, Shiga K, Takahashi H, Takeyama H. High serum levels of interleukin-6 in patients with advanced or metastatic colorectal cancer: the effect on the outcome and the response to chemotherapy plus bevacizumab. Surg Today. 2017;47(4):483-89.

Kruk J, Aboul-Enein HY. Reactive Oxygen and Nitrogen Species in Carcinogenesis: Implications of Oxidative Stress on the Progression and Development of Several Cancer Types. Mini Rev Med Chem. 2017;17(11):904-19.

Aldeen YM, Habeeb P, Jawad AH. Study Oxidative Stress Statues In Hypertension Women. Baghdad Sci J. 2016;13(2):407-13.

Rezatabar S, Karimian A, Rameshknia V, Parsian H, Majidinia M, Kopi TA, et al. RAS/MAPK signaling functions in oxidative stress, DNA damage response and cancer progression. J Cell Physiol. 2019;234(9):14951-65.

Kryston TB, Georgiev AB, Pissis P, Georgakilas AG. Role of oxidative stress and DNA damage in human carcinogenesis. Mutat Res. 2011;711(1-2):193-201.

Leung EY, Crozier JE, Talwar D, O'Reilly DS, McKee RF, Horgan PG, et al. Vitamin antioxidants, lipid peroxidation, tumour stage, the systemic inflammatory response and survival in patients with colorectal cancer. Int J Cancer. 2008;123(10):2460-464.

Fu XL, Duan W, Su CY, Mao FY, Lv YP, Teng YS, et al. Interleukin 6 induces M2 macrophage differentiation by STAT3 activation that correlates with gastric cancer progression. Cancer Immunol Immunother. 2017;66(12):1597-608.

Kabir S, Daar GA. Serum levels of interleukin-1, interleukin-6 and tumour necrosis factor-alpha in patients with gastric carcinoma. Cancer Lett. 1995;95(1-2):207-12.

Guo L, Ou JL, Zhang T, Ma L, Qu LF. Effect of expressions of tumor necrosis factor alpha and interleukin 1B on peritoneal metastasis of gastric cancer. Tumour Biol. 2015;36(11):8853-60.

Al Obeed OA, Alkhayal KA, Al Sheikh A, Zubaidi AM, Vaali-Mohammed MA, Boushey R, et al. Increased expression of tumor necrosis factor-alpha is associated with advanced colorectal cancer stages. World J Gastroenterol. 2014;20(48):18390-6.

Mojic M, Takeda K, Hayakawa Y. The Dark Side of IFN-γ: Its Role in Promoting Cancer Immunoevasion. Int J Mol Sci. 2018;19(1):89.

Tseng PC, Chen CL, Shan YS, Lin CF. An increase in galectin-3 causes cellular unresponsiveness to IFN-gamma-induced signal transduction and growth inhibition in gastric cancer cells. Oncotarget. 2016;7(12):15150-60.

Xu YH, Li ZL, Qiu SF. IFN-gamma Induces Gastric Cancer Cell Proliferation and Metastasis Through Upregulation of Integrin beta3-Mediated NF-kappaB Signaling. Transl Oncol. 2018;11(1):182-92.

Hall C, Clarke L, Pal A, Buchwald P, Eglinton T, Wakeman C, et al. A Review of the Role of Carcinoembryonic Antigen in Clinical Practice. Ann Coloproctol. 2019;35(6):294-305.