Prognostic significance of mitochondrial oxidative phosphorylation complexes: Therapeutic target in the treatment of retinoblastoma

• Alteration in mtOXPHOS activity is a key feature of malignant cells
• Loss of mitochondrial complex I may act as an independent prognostic marker in Rb
• Aberrant mitochondrial OXPHOS complexes may play a key role in controlling tumor cells life and proliferation.

PurposeAltered 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).MethodsImmunohistochemistry was performed on 109 primary enucleated retinoblastoma tissues for mitochondrial OXPHOS complexes and their expression was confirmed by western blotting.ResultsHistopathological 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).ConclusionsThis 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.Financial disclosureThe author(s) have no proprietary or commercial interest in any materials discussed in this article.