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European Journal of Medical Research

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Open Access 01-12-2023 | Urothelial Cancer | Research

Systematic oxidative stress indices predicts prognosis in patients with urothelial carcinoma of the upper urinary tract after radical nephroureterectomy

Authors: Jianyong Liu, Shicong Lai, Pengjie Wu, Jiawen Wang, Jianye Wang, Jianlong Wang, Yaoguang Zhang

Published in: European Journal of Medical Research | Issue 1/2023

Abstract

Background

Oxidative stress plays an important role in the occurrence and development of malignancy. However, the relationship between oxidative stress and upper urinary tract urothelial carcinoma (UTUC) prognosis remains elusive. This study aimed to evaluate the prognostic value of systematic oxidative stress indices as a predictor of patient outcomes in UTUC after radical nephroureterectomy.

Methods

Clinical data for 483 patients with UTUC who underwent radical nephroureterectomy were analyzed. Patients were categorized according to an optimal value of systematic oxidative stress indices (SOSIs), including fibrinogen (Fib), gamma-glutamyl transpeptidase (γ-GGT), creatinine (CRE), lactate dehydrogenase (LDH) and albumin (ALB). Kaplan–Meier analyses were used to investigate associations of SOSIs with overall survival (OS) and progression-free survival (PFS). Moreover, associations between SOSIs and OS and PFS were assessed with univariate and multivariate analyses.

Results

High values of Fib, γ-GGT, CRE, and LDH, and low values of ALB were associated with reduced OS. SOSIs status correlated with age, tumor site, surgical approach, hydronephrosis, tumor size, T stage, and lymph node status. The Kaplan–Meier survival analysis showed a significant discriminatory ability for death and progression risks in the two groups based on SOSIs. Multivariate Cox proportional hazards models showed that SOSIs were an independent prognostic indicator for OS (p = 0.007) and PFS (p = 0.021). SOSIs and clinical variables were selected to establish a nomogram for OS. The 1-, 3-, and 5-year AUC values were 0.77, 0.78, and 0.81, respectively. Calibration curves of the nomogram showed high consistencies between the predicted and observed survival probability. Decision curve analysis curves showed that the nomogram could well predict the 1‐year, 3-year, and 5‐year OS.

Conclusions

SOSIs are an independent unfavorable predictor of OS and PFS in patients diagnosed with UTUC undergoing RNU. Therefore, incorporating SOSIs into currently available clinical parameters may improve clinical decision-making.

Rouprêt M, Babjuk M, Burger M, Capoun O, Cohen D, Compérat EM, Cowan NC, Dominguez-Escrig JL, Gontero P, Hugh Mostafid A, et al. European association of urology guidelines on upper urinary tract urothelial carcinoma: 2020 update. Eur Urol. 2021;79(1):62–79.PubMedCrossRef

Vitaly M, Shahrokh FS, Surena FM, Kamat MA, Zigeuner R, Kikuchi E, Lotan Y, Weizer A, Raman JD, Wood CG. Outcomes of radical nephroureterectomy: a series from the upper tract urothelial carcinoma collaboration. Cancer. 2009;115(6):1224–33.CrossRef

Lughezzani G, Burger M, Margulis V, Matin SF, Novara G, Roupret M, Shariat SF, Wood CG, Zigeuner R. Prognostic factors in upper urinary tract urothelial carcinomas: a comprehensive review of the current literature. Eur Urol. 2012;62(1):100–14.PubMedCrossRef

Abouassaly R, Alibhai SMH, Shah N, Timilshina N, Fleshner N, Finelli A. Troubling outcomes from population-level analysis of surgery for upper tract urothelial carcinoma. Urology. 2010;76(4):895–901.PubMedCrossRef

Jeldres C, Sun M, Isbarn H, Lughezzani G, Budäus L, Alasker A, Shariat SF, Lattouf J-B, Widmer H, Pharand D, et al. A population-based assessment of perioperative mortality after nephroureterectomy for upper-tract urothelial carcinoma. Urology. 2010;75(2):315–20.PubMedCrossRef

Canli Ö, Nicolas AM, Gupta J, Finkelmeier F, Goncharova O, Pesic M, Neumann T, Horst D, Löwer M, Sahin U, et al. Myeloid cell-derived reactive oxygen species induce epithelial mutagenesis. Cancer Cell. 2017. https://doi.org/10.1016/j.ccell.2017.11.004.CrossRefPubMed

Srinivas US, Tan BWQ, Vellayappan BA, Jeyasekharan AD. ROS and the DNA damage response in cancer. Redox Biol. 2019;25: 101084.PubMedCrossRef

Slopovsky J, Kucharska J, Obertova J, Mego M, Kalavska K, Cingelova S, Svetlovska D, Gvozdjakova A, Furka S, Palacka P. Plasma thiobarbituric acid reactive substances predicts survival in chemotherapy naïve patients with metastatic urothelial carcinoma. Transl Oncol. 2021;14(1): 100890.PubMedCrossRef

Chang IW, Lin VC-H, Hung C-H, Wang H-P, Lin Y-Y, Wu W-J, Huang C-N, Li C-C, Li W-M, Wu J-Y, et al. GPX2 underexpression indicates poor prognosis in patients with urothelial carcinomas of the upper urinary tract and urinary bladder. World J Urol. 2015;33(11):1777–89.PubMedCrossRef

10.

Teixeira-Gomes A, Laffon B, Valdiglesias V, Gostner JM, Felder T, Costa C, Madureira J, Fuchs D, Teixeira JP, Costa S. Exploring early detection of frailty syndrome in older adults: evaluation of oxi-immune markers, clinical parameters and modifiable risk factors. Antioxidants. 2021. https://doi.org/10.3390/antiox10121975.CrossRefPubMedPubMedCentral

11.

Periasamy S, Hsu D-Z, Fu Y-H, Liu M-Y. Sleep deprivation-induced multi-organ injury: role of oxidative stress and inflammation. EXCLI J. 2015;14:672–83.PubMedPubMedCentral

12.

Sandesc M, Rogobete AF, Bedreag OH, Dinu A, Papurica M, Cradigati CA, Sarandan M, Popovici SE, Bratu LM, Bratu T, et al. Analysis of oxidative stress-related markers in critically ill polytrauma patients: an observational prospective single-center study. Bosn J Basic Med Sci. 2018;18(2):191–7.PubMedPubMedCentralCrossRef

13.

Ahmed S, Zahoor A, Ibrahim M, Younus M, Nawaz S, Naseer R, Akram Q, Deng C-L, Ojha SC. Enhanced efficacy of direct-acting antivirals in hepatitis C patients by coadministration of black cumin and ascorbate as antioxidant adjuvants. Oxid Med Cell Longev. 2020;2020:7087921.PubMedPubMedCentralCrossRef

14.

Becatti M, Marcucci R, Bruschi G, Taddei N, Bani D, Gori AM, Giusti B, Gensini GF, Abbate R, Fiorillo C. Oxidative modification of fibrinogen is associated with altered function and structure in the subacute phase of myocardial infarction. Arterioscler Thromb Vasc Biol. 2014;34(7):1355–61.PubMedCrossRef

15.

McLarnon JG. A leaky blood-brain barrier to fibrinogen contributes to oxidative Damage in Alzheimer’s Disease. Antioxidants. 2021. https://doi.org/10.3390/antiox11010102.CrossRefPubMedPubMedCentral

16.

White NJ, Wang Y, Fu X, Cardenas JC, Martin EJ, Brophy DF, Wade CE, Wang X, St John AE, Lim EB, et al. Post-translational oxidative modification of fibrinogen is associated with coagulopathy after traumatic injury. Free Radic Biol Med. 2016;96:181–9.PubMedPubMedCentralCrossRef

17.

Cao Y, Deng S, Yan L, Gu J, Mao F, Xue Y, Zheng C, Yang M, Liu H, Liu L, et al. An oxidative stress index-based score for prognostic prediction in colorectal cancer patients undergoing surgery. Oxid Med Cell Longev. 2021;2021:6693707.PubMedPubMedCentralCrossRef

18.

Ping L, Gao Y, He Y, Wang X, Bai B, Huang C, Huang H. Systematic oxidative stress indexes associated with the prognosis in patients with t lymphoblastic lymphoma/leukemia. Oxid Med Cell Longev. 2022;2022:2679154.PubMedPubMedCentralCrossRef

19.

Zhang K, Ping L, Du T, Wang Y, Sun Y, Liang G, Wang X, Xie X, Wei W, Xiao X, et al. A novel systematic oxidative stress score predicts the prognosis of patients with operable breast cancer. Oxid Med Cell Longev. 2021;2021:9441896.PubMedPubMedCentralCrossRef

20.

Sies H, editor. Oxidative Stress. London: Academic Press; 1985. p. 1–507.CrossRef

21.

Sies H. Oxidative stress: a concept in redox biology and medicine. Redox Biol. 2015;4:180–3.PubMedPubMedCentralCrossRef

22.

Ďuračková Z. Some current insights into oxidative stress. Physiol Res. 2010;59(4):459–69.PubMedCrossRef

23.

Gill JG, Piskounova E, Morrison SJ. Cancer, oxidative stress, and metastasis. Cold Spring Harb Symp Quant Biol. 2016;81:163–75.PubMedCrossRef

24.

Elchuri S, Oberley TD, Qi W, Eisenstein RS, Jackson Roberts L, Van Remmen H, Epstein CJ, Huang T-T. CuZnSOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life. Oncogene. 2005;24(3):367–80.PubMedCrossRef

25.

Van Remmen H, Ikeno Y, Hamilton M, Pahlavani M, Wolf N, Thorpe SR, Alderson NL, Baynes JW, Epstein CJ, Huang T-T, et al. Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging. Physiol Genomics. 2003;16(1):29–37.PubMedCrossRef

26.

McLoughlin MR, Orlicky DJ, Prigge JR, Krishna P, Talago EA, Cavigli IR, Eriksson S, Miller CG, Kundert JA, Sayin VI, et al. TrxR1, Gsr, and oxidative stress determine hepatocellular carcinoma malignancy. Proc Natl Acad Sci U S A. 2019;116(23):11408–17.PubMedPubMedCentralCrossRef

27.

Papachristodoulou A, Rodriguez-Calero A, Panja S, Margolskee E, Virk RK, Milner TA, Martina LP, Kim JY, Di Bernardo M, Williams AB, et al. NKX3.1 localization to mitochondria suppresses prostate cancer initiation. Cancer Disc. 2021;11(9):2316–33.CrossRef

28.

Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med. 2010;49(11):1603–16.PubMedPubMedCentralCrossRef

29.

Margis R, Dunand C, Teixeira FK, Margis-Pinheiro M. Glutathione peroxidase family - an evolutionary overview. FEBS J. 2008;275(15):3959–70.PubMedCrossRef

30.

Heffron SP, Parastatidis I, Cuchel M, Wolfe ML, Tadesse MG, Mohler ER, Ischiropoulos H, Rader DJ, Reilly MP. Inflammation induces fibrinogen nitration in experimental human endotoxemia. Free Radic Biol Med. 2009;47(8):1140–6.PubMedPubMedCentralCrossRef

31.

Wang M, Zhang G, Zhang Y, Cui X, Wang S, Gao S, Wang Y, Liu Y, Bae JH, Yang W-H, et al. Fibrinogen alpha chain knockout promotes tumor growth and metastasis through integrin-AKT signaling pathway in lung cancer. Mol Cancer Res. 2020;18(7):943–54.PubMedCrossRef

32.

Guo Y, Liu J, Zhang W, Xiao S, Zheng G, Liu S, Guo M, Zhang H, Feng F. Prognostic value of fibrinogen and lymphocyte count in intermediate and high risk gastrointestinal stromal tumors. Cancer Manag Res. 2020;12:8149–57.PubMedPubMedCentralCrossRef

33.

Sui J, Noubouossie DF, Gandotra S, Cao L. Elevated plasma fibrinogen is associated with excessive inflammation and disease Severity in COVID-19 patients. Front Cell Infect Microbiol. 2021;11: 734005.PubMedPubMedCentralCrossRef

34.

Papila Kundaktepe B, Papila C. The clinical significance of preoperative plasma fibrinogen levels and platelet counts in resectable colon cancer. World J Surg Oncol. 2021;19(1):69.PubMedPubMedCentralCrossRef

35.

Chung KH, Lee J-C, Lee J, Cho I-K, Kim J, Jang W, Yoo BC, Hwang J-H. Serum fibrinogen as a diagnostic and prognostic biomarker for pancreatic ductal adenocarcinoma. Pancreatology. 2020;20(7):1465–71.PubMedCrossRef

36.

Xu H, Ai J-Z, Tan P, Lin T-H, Jin X, Gong L-N, Lei H-R, Yang L, Wei Q. Pretreatment elevated fibrinogen level predicts worse oncologic outcomes in upper tract urothelial carcinoma. Asian J Androl. 2020;22(2):177–83.PubMedCrossRef

37.

Brosnan JT, Brosnan ME. Creatine metabolism and the urea cycle. Mol Genet Metab. 2010;100(Suppl 1):S49–52.PubMedCrossRef

38.

Wyss M, Kaddurah-Daouk R. Creatine and creatinine metabolism. Physiol Rev. 2000;80(3):1107–213.PubMedCrossRef

39.

Kashani K, Rosner MH, Ostermann M. Creatinine: from physiology to clinical application. Eur J Intern Med. 2020. https://doi.org/10.1016/j.ejim.2019.10.025.CrossRefPubMedPubMedCentral

40.

Irazabal MV, Torres VE. Reactive oxygen species and redox signaling in chronic kidney disease. Cells. 2020. https://doi.org/10.3390/cells9061342.CrossRefPubMedPubMedCentral

41.

Whitfield JB. Gamma glutamyl transferase. Crit Rev Clin Lab Sci. 2001;38(4):263–355.PubMedCrossRef

42.

Lee D-H, Blomhoff R, Jacobs DR. Is serum gamma glutamyltransferase a marker of oxidative stress? Free Radic Res. 2004;38(6):535–9.PubMedCrossRef

43.

Zhang H, Forman HJ. Redox regulation of gamma-glutamyl transpeptidase. Am J Respir Cell Mol Biol. 2009;41(5):509–15.PubMedPubMedCentralCrossRef

44.

Yang D, Wu H, Nong W, Zheng M, Li A, Wang Y, Li M, Chen Q, Yuan S, Yu J, et al. A new model based on gamma-glutamyl transpeptidase to platelet ratio (GPR) predicts prognostic outcome after curative resection of solitary hepatocellular carcinoma. Clin Res Hepatol Gastroenterol. 2021;45(5): 101509.PubMedCrossRef

45.

Bozkaya Y, Yazıcı O. Prognostic significance of gamma-glutamyl transferase in patients with metastatic non-small cell lung cancer. Expert Rev Mol Diagn. 2019;19(3):267–72.PubMedCrossRef

46.

Xiao B, Peng J, Tang J, Deng Y, Zhao Y, Wu X, Ding P, Lin J, Pan Z. Serum Gamma Glutamyl transferase is a predictor of recurrence after R0 hepatectomy for patients with colorectal cancer liver metastases. Therap Adv Med Oncol. 2020;12:1758835920947971.

47.

Ždralević M, Brand A, Di Ianni L, Dettmer K, Reinders J, Singer K, Peter K, Schnell A, Bruss C, Decking S-M, et al. Double genetic disruption of lactate dehydrogenases A and B is required to ablate the “Warburg effect” restricting tumor growth to oxidative metabolism. J Biol Chem. 2018;293(41):15947–61.PubMedPubMedCentralCrossRef

48.

Li X, Zhang C, Zhao T, Su Z, Li M, Hu J, Wen J, Shen J, Wang C, Pan J, et al. Lysine-222 succinylation reduces lysosomal degradation of lactate dehydrogenase a and is increased in gastric cancer. J Exp Clin Cancer Res. 2020;39(1):172.PubMedPubMedCentralCrossRef

49.

Le A, Cooper CR, Gouw AM, Dinavahi R, Maitra A, Deck LM, Royer RE, Vander Jagt DL, Semenza GL, Dang CV. Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression. Proc Natl Acad Sci U S A. 2010;107(5):2037–42.PubMedPubMedCentralCrossRef

50.

Roche M, Rondeau P, Singh NR, Tarnus E, Bourdon E. The antioxidant properties of serum albumin. FEBS Lett. 2008;582(13):1783–7.PubMedCrossRef

51.

Pradere B, D’Andrea D, Schuettfort VM, Foerster B, Quhal F, Mori K, Abufaraj M, Margulis V, Deuker M, Briganti A, et al. Pre-therapy serum albumin-to-globulin ratio in patients treated with neoadjuvant chemotherapy and radical nephroureterectomy for upper tract urothelial carcinoma. World J Urol. 2021;39(7):2567–77.PubMedCrossRef

52.

Iacovino ML, Miceli CC, De Felice M, Barone B, Pompella L, Chiancone F, Di Zazzo E, Tirino G, Della Corte CM, Imbimbo C, et al. Novel therapeutic opportunities in neoadjuvant setting in urothelial cancers: a new horizon opened by molecular classification and immune checkpoint inhibitors. Int J Mol Sci. 2022. https://doi.org/10.3390/ijms23031133.CrossRefPubMedPubMedCentral

53.

Barone B, Calogero A, Scafuri L, Ferro M, Lucarelli G, Di Zazzo E, Sicignano E, Falcone A, Romano L, De Luca L, et al. Immune checkpoint inhibitors as a neoadjuvant/adjuvant treatment of muscle-invasive bladder cancer: a systematic review. Cancers. 2022. https://doi.org/10.3390/cancers14102545.CrossRefPubMedPubMedCentral

Title: Systematic oxidative stress indices predicts prognosis in patients with urothelial carcinoma of the upper urinary tract after radical nephroureterectomy
Authors: Jianyong Liu
Shicong Lai
Pengjie Wu
Jiawen Wang
Jianye Wang
Jianlong Wang
Yaoguang Zhang
Publication date: 01-12-2023
Publisher: BioMed Central
Keywords: Urothelial Cancer
Urothelial Cancer
Published in: European Journal of Medical Research / Issue 1/2023
Electronic ISSN: 2047-783X
DOI: https://doi.org/10.1186/s40001-023-01295-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Systematic oxidative stress indices predicts prognosis in patients with urothelial carcinoma of the upper urinary tract after radical nephroureterectomy

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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Correction: Protective effects of paraoxonase-1, vitamin E and selenium, and oxidative stress index on the susceptibility of low density lipoprotein to oxidation in diabetic patients with/without coronary artery disease