Overexpression of NDUFA4L2 is associated with poor prognosis in patients with colorectal cancer

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Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer‐related death in the United States. Almost one third of CRC patients have metastatic disease at diagnosis.1 Over the past 30 years, the incidence and mortality of CRC have increased significantly. Early diagnosis, degree of malignancy and prognosis of CRC have become a hot field in biomedical research. Recently, advances in understanding of tumour biology have led to the development of targeted therapies, allowing progress in the treatment of CRC.2
The mitochondrial NDUFA4L2 (NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4‐like 2, also called NADH‐ubiquinone oxidoreductase MLRQ subunit homologue), a negative regulator of mitochondrial complex I, has been identified as a hypoxia‐inducible factor‐1 (HIF‐1) target gene and localized in mitochondria.4 It was previously described using mRNA array technology that NDUFA4L2 is overexpressed in von Hippel‐Lindau‐deficient cell lines and tumours,5 as well as in neuroblastoma cells in hypoxia7 and in pathophysiological conditions such as rheumatoid arthritis.8 Fu et al. reported that NDUFA4L2 is the gene that is overexpressed to the greatest extent in the human clear cell renal cell carcinoma (ccRCC) data sets in Oncomine. Especially, NDUFA4L2 transcript levels are about 68‐fold higher in the TRAnsgenic model of Cancer of the Kidney transgenic positive kidneys compared with transgenic negative kidneys.9 However, NDUFA4L2 expression and its clinical significance in CRC have not yet been reported; especially about its effects on CRC progression. In this study, we evaluated NDUFA4L2 expression in clinical CRC tissue specimens, determined its correlation with clinicopathological characteristics and explored their clinical significance in CRC tumours obtained from 150 surgically treated patients with more than 5 years of median follow‐up data.

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