title: Prognostic significance of mitochondrial oxidative phosphorylation complexes: Therapeutic target in the treatment of retinoblastoma.
abstract: OBJECTIVE
  Altered energy metabolism plays an important role in the development and progression of cancer. The objective of this study was to elucidate the role of mitochondrial oxidative phosphorylation complexes and their prognostic significance in retinoblastoma (Rb).
  
  
  METHODS
  Immunohistochemistry was performed on 109 primary enucleated retinoblastoma tissues for mitochondrial OXPHOS complexes and their expression was confirmed by western blotting.
  
  
  RESULTS
  Histopathological high risk factors (HRFs) were identified in 42.2% cases. Mitochondrial OXPHOS complexes III, IV and V were expressed in more than 50% of primary retinoblastoma cases each whereas mitochondrial complex I was expressed in only 29/109 (26.60%) cases by immunohistochemistry. Loss of mitochondrial complex I correlated well with poor tumor differentiation and tumor invasion (p < 0.05) whereas expression of mitochondrial complexes III, IV and V was associated with better survival (Kaplan-Meier method).
  
  
  CONCLUSIONS
  This was the first study predicting a relevant role of mitochondrial OXPHOS complexes and highlights the prognostic significance with patient outcome in retinoblastoma. Loss of mitochondrial complex I immunoexpression could prove to be a useful independent prognostic biomarker to identify high risk retinoblastoma patients. Differential expression of these mitochondrial complexes is a novel finding and may be used as an attractive future anticancer target in primary retinoblastoma tumors.
  
  
  BACKGROUND
  The author(s) have no proprietary or commercial interest in any materials discussed in this article.
authors.affiliation: Department of Ocular Pathology, Dr. R. P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Lata
authors.initials: L
authors.lastname: Singh
authors.affiliation: Functional Genomics Unit, Institute of Genomics and Integrative Biology, Mall Road, New Delhi, India.
authors.forename: Neeru
authors.initials: N
authors.lastname: Saini
authors.affiliation: Department of Medical Oncology, IRCH, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Sameer
authors.initials: S
authors.lastname: Bakhshi
authors.affiliation: Department of Ophthalmology, Dr. R. P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Neelam
authors.initials: N
authors.lastname: Pushker
authors.affiliation: Department of Ocular Pathology, Dr. R. P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Seema
authors.initials: S
authors.lastname: Sen
authors.affiliation: Department of Ocular Microbiology, Dr. R. P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Anjana
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Department of Ocular Biochemistry, Dr. R. P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Jasbir
authors.initials: J
authors.lastname: Kaur
authors.affiliation: Department of Ocular Pathology, Dr. R. P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India. Electronic address: dr_skashyap@hotmail.com.
authors.forename: Seema
authors.initials: S
authors.lastname: Kashyap
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009097:Multienzyme Complexes / Q000032:analysis*; D010085:Oxidative Phosphorylation; D010088:Oxidoreductases / Q000032:analysis*; D011379:Prognosis; D012175:Retinoblastoma / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D009097:Multienzyme Complexes; D010088:Oxidoreductases
keywords: Immunohistochemistry; Oxidative phosphorylation complexes; Retinoblastoma; Western blotting