JOURNAL of
ONCOLOGICAL
SCIENCES

ORIGINAL RESEARCH ARTICLE

Relationship Between Xanthine Oxidoreductase Activity and BRCA1 Levels in Patients with Stage IIIA and IIIB Non-Small Cell Lung Cancer Being Treated with Neoadjuvant Chemotherapy
Received Date : 16 Oct 2019
Accepted Date : 09 Apr 2020
Available Online : 24 Jun 2020
Doi: 10.37047/jos.2019-71890 - Article's Language: EN
J Oncol Sci.2020;6(2):71-7
This is an open access article under the CC BY-NC-ND license
ABSTRACT
Objective: Lung cancer is the leading cause of cancer-related death worldwide. Treatment in locally advanced non-small cell lung cancer (NSCLC) is heterogeneous. The cure rates after complete surgical resections are not as good as expected. A better understanding of the biology of NSCLC might allow the selection of appropriate treatment. Only a few studies have been carried out on the prognostic value of xanthine oxidoreductase (XOR) and BRCA1 in lung cancer. Material and Methods: In this study, 35 patients with stage IIIA and stage IIIB of NSCLC were included. They were operated in Baskent Ankara and Adana hospitals and received neoadjuvant chemotherapy. The regular follow-up of all the patients was done in Baskent University Medical Oncology, Thoracic Surgery Department. The clinical and histopathological parameters (age, gender, stage, smoking history, performance status, and neoadjuvant chemotherapy), along with the immunohistochemical study of BRCA1 and XOR staining, were examined, and correlated with survival outcomes. Results: Median overall survival time was reported as 38.5 months, and 5-year survival rate was 33%. The presence of BRCA1 was positively associated with shorter overall survival in stage III lung cancer patients, who were followed up with the neoadjuvant platinum-based chemotherapy regime (p<0.05). There was no relation between XOR activity and overall survival outcomes. Conclusion: BRCA1-positive status might be prognostic in patients with Stage IIIA and IIIB of NSCLC.
KAYNAKLAR
  1. Battelli MG, Polito L, Bortolotti M, Bolognesi A. Xanthine oxidoreductase-derived reactive species: physiological and pathological effects. Oxid Med Cell Longev. 2016;2016: 3527579. [Crossref]  [PubMed]  [PMC] 
  2. Xu X, Rao G, Li Y. Xanthine oxidoreductase is required for genotoxic stress-induced NKG2D ligand expression and gemcitabine-mediated antitumor activity. Oncotarget. 2016;7(37):59220-59235. [Crossref]  [PubMed]  [PMC] 
  3. Battelli MG, Polito L, Bortolotti M, Bolognesi A. Xanthine oxidoreductase in cancer: more than a differentiation marker. Cancer Med. 2016;5(3):546-557. [Crossref]  [PubMed]  [PMC] 
  4. Konno H, Minamiya Y, Saito H, et al. Acquired xanthine dehydrogenase expression shortens survival in patients with resected adenocarcinoma of lung. Tumour Biol. 2012;33(5):1727-1732. [Crossref]  [PubMed] 
  5. Fini MA, Monks J, Farabaugh SM, Wright RM. Contribution of xanthine oxidoreductase to mammary epithelial and breast cancer cell differentiation in part modulates inhibitor of differentiation-1. Mol Cancer Res. 2011;9(9): 1242-1254. [Crossref]  [PubMed]  [PMC] 
  6. Owen D, Sheffield BS, Ionescu D, Churg A. Loss of BRCA1-associated protein 1 (BAP1) expression is rare in non-small cell lung cancer. Hum Pathol. February 2017;60:82-85. [Crossref]  [PubMed] 
  7. Wilson A, Yakovlev VA. Cells redox environment modulates BRCA1 expression and DNA homologous recombination repair. Free Radic Biol Med. December 2016;101:190-201. [Crossref]  [PubMed] 
  8. Shen C, Wang Y, Wei P, Du X. BRCA1-associated protein 1 deficiency in lung adenocarcinoma predicts poor outcome and increased tumor invasion. BMC Cancer. 2016;16(1):670. [Crossref]  [PubMed]  [PMC] 
  9. Su C, Zhou S, Zhang L, et al. ERCC1 RRM1 and BRCA1 mRNA expression levels and clinical outcome of advanced non-small cell lung cancer. Med Oncol. 2011;28(4):1411-1417. [Crossref]  [PubMed] 
  10. Smirnow S, Pashkevich A, Liundyseheva V, Babenko A, Smolyakova R. Heterogeneity of excision repair cross-complementation group 1 gene expression in non-small-cell lung cancer patients. Mol Clin Oncol. 2015;3(1):227-331. [Crossref]  [PubMed]  [PMC] 
  11. Kan C, Zhang J .BRCA1 Mutation: a predictive marker for radiation therapy? Int J Radiat Oncol Biol Phys. 2015;93(2):281-293. [Crossref]  [PubMed]  [PMC] 
  12. Lafarge S, Sylvian V, Ferrara M, Bignon YJ. Inhibition of BRCA1 leads to increased chemoresistance to microtubule-interfering agents, an affect that involves the JNK pathway. Oncogene. 2001;20(45):6597-6606. [Crossref]  [PubMed] 
  13. Linder N, Haglund C, Lundin M, et al. Decreased xanthine oxidoreductase is a predictor of poor prognosis in early-stage gastric cancer. J Clin Pathol. 2006;59(9):965-971. [Crossref]  [PubMed]  [PMC] 
  14. Pápay J, Sápi Z, Egri G, et al. Platinum-based chemotherapy in lıng cancer affects the expression of certain biomarkers including ERCC1. Pathol Oncol Res. 2009;15(3):445-450. [Crossref]  [PubMed] 
  15. Taron M, Rosell R, Felip E, et al. BRCA1 mRNA expression levels as an indicator of chemoresistance in lung cancer. Hum Mol Genet. 2004;13(20):2443-2449. [Crossref]  [PubMed] 
  16. Rosell R, Moran T, Cardenal F, et al. Predictive biomarkers in the management of EGFR mutant lung cancer. Ann N Y Acad Sci. October 2010;1210:45-52. [Crossref]  [PubMed] 
  17. Rosell R, Perez-Roca L, Sanchez JJ, et al. Customised treatment in non-small-cell lung cancer based on EGFR mutations and BRCA1 mRNA expression. PloS One. 2009;4(5):e5133. [Crossref]  [PubMed]  [PMC] 
  18. Kennedy RD, Quinn JE, Johnston PG, Harkin DP. BRCA1: mechanisms of inactivation and implications for management of patients. Lancet. 2002;360(9338):1007-1014. [Crossref]  [PubMed] 
  19. Linder N, Lundin J, Isola J, Lundin M, Raivio KO, Joensuu H. Down-regulated xanthine oxidoreductase is a future of aggressive breast cancer. Clin Cancer Res. 2005;11(12);4372-4381. [Crossref]  [PubMed] 
  20. Lewin I, Lewin R, Bray RC. Xanthine oxidase activity during mammary carcinogenesis in mice. Nature. 1957;180(4589):763-764. [Crossref]  [PubMed]