Singh Lata, Saini Neeru, Bakhshi Sameer, Pushker Neelam, Sen Seema, Sharma Anjana, Kaur Jasbir, Kashyap Seema
Department of Ocular Pathology, Dr. R. P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.
Functional Genomics Unit, Institute of Genomics and Integrative Biology, Mall Road, New Delhi, India.
Mitochondrion. 2015 Jul;23:55-63. doi: 10.1016/j.mito.2015.06.001. Epub 2015 Jun 10.
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).
Immunohistochemistry was performed on 109 primary enucleated retinoblastoma tissues for mitochondrial OXPHOS complexes and their expression was confirmed by western blotting.
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).
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.
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
能量代谢改变在癌症的发生和发展中起重要作用。本研究的目的是阐明线粒体氧化磷酸化复合物在视网膜母细胞瘤（Rb）中的作用及其预后意义。
对109例原发性摘除的视网膜母细胞瘤组织进行免疫组织化学检测线粒体氧化磷酸化复合物，并通过蛋白质印迹法确认其表达。
42.2%的病例中发现了组织病理学高危因素（HRFs）。线粒体氧化磷酸化复合物III、IV和V在超过50%的原发性视网膜母细胞瘤病例中均有表达，而通过免疫组织化学检测，线粒体复合物I仅在29/109（26.60%）的病例中表达。线粒体复合物I的缺失与肿瘤分化差和肿瘤侵袭密切相关（p<0.05），而线粒体复合物III、IV和V的表达与更好的生存率相关（Kaplan-Meier法）。
这是第一项预测线粒体氧化磷酸化复合物相关作用的研究，并突出了其在视网膜母细胞瘤患者预后中的意义。线粒体复合物I免疫表达的缺失可能被证明是一种有用的独立预后生物标志物，用于识别高危视网膜母细胞瘤患者。这些线粒体复合物的差异表达是一个新发现，可能作为原发性视网膜母细胞瘤肿瘤未来有吸引力的抗癌靶点。
作者对本文讨论的任何材料均无所有权或商业利益。
