title: Prognostic significance of NADPH oxidase-4 as an indicator of reactive oxygen species stress in human retinoblastoma.
abstract: BACKGROUND
  Reactive oxygen species (ROS) have been shown to enhance the proliferation of cancer cells. NADPH oxidases (NOX4) are a major intracellular source of ROS and are found to be associated with cancer and tumor cell invasion. Therefore, the purpose of this study is to evaluate the expression of NOX4 protein in human retinoblastoma.
  
  
  METHODS
  Immunohistochemical expression of NOX4 protein was analyzed in 109 specimens from prospective cases of retinoblastoma and then correlated with clinicopathological parameters and patient survival. Western blotting confirmed and validated the immunoreactivity of NOX4 protein.
  
  
  RESULTS
  In our study we found a male preponderance (55.9 %), and 25/109 (22.9 %) were bilateral. Massive choroidal invasion was the histopathological high-risk factor (HRF) most frequently observed, in 42.2 % of the cases. NOX4 protein was expressed in 67.88 % (74/109) of primary retinoblastoma cases and was confirmed by Western blotting. NOX4 was statistically significant with massive choroidal invasion and pathological TNM staging. There was a statistically significant difference in overall survival in patients with NOX4 expression (p = 0.0461).
  
  
  CONCLUSIONS
  This is the first study to show the expression of NOX4 protein in retinoblastoma tumors. Hence, a retinoblastoma tumor may exhibit greater ROS stress. This protein may prove to be useful as a future therapeutic target for improving the management of retinoblastoma.
authors: Department of Ocular Pathology, Dr. R.P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.
authors: Lata
authors: L
authors: Singh
authors: Functional Genomics Unit, Institute of Genomics and Integrative Biology, Mall Road, New Delhi, India.
authors: Neeru
authors: N
authors: Saini
authors: Department of Ophthalmology, Dr. R.P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.
authors: Neelam
authors: N
authors: Pushker
authors: Department of Ocular Pathology, Dr. R.P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.
authors: Seema
authors: S
authors: Sen
authors: Department of Ocular Microbiology, Dr. R.P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.
authors: Anjana
authors: A
authors: Sharma
authors: Department of Ocular Pathology, Dr. R.P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India. dr_skashyap@hotmail.com.
authors: Seema
authors: S
authors: Kashyap
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D002675:Child, Preschool; D002829:Choroid / Q000473:pathology; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000032:analysis*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D018384:Oxidative Stress; D011379:Prognosis; D011446:Prospective Studies; D017382:Reactive Oxygen Species; D019572:Retinal Neoplasms / Q000201:enzymology* / Q000473:pathology*; D012175:Retinoblastoma / Q000201:enzymology* / Q000473:pathology*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D017382:Reactive Oxygen Species; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human
keywords: Histopathological high-risk factors; Immunohistochemistry; NADPH oxidase; Retinoblastoma