Expression and significance of ETFDH in hepatocellular carcinoma.

The ETFDH (electron transfer flavoprotein dehydrogenase) gene mutations are reported to be a major cause of riboflavin-responsive multiple acyl-coenzyme A dehydrogenation deficiency (MADD). However, the role of ETFDH in the prognosis of hepatocellular carcinoma (HCC) remains unclear. The aim of this study was to investigate the expression of ETFDH in HCC. Immunohistochemical staining of the 207 HCC tissue microarray showed that expression of ETFDH was significantly decreased in HCC compared with the matching noncancerous hepatic tissues (P < 0.001). Moreover, ETFDH expression levels were found to be correlated with AFP levels (P = 0.011). Intriguingly, ETFDH expression levels were significantly lower in poorly differentiated or undifferentiated HCCs as compared to the well or moderately differentiated cases (P =  0.001). Kaplan-Meier analysis revealed that low tumor expression of ETFDH was associated with a poorer overall survival in patients with HCC (P =  0.024). Furthermore, multivariate analysis showed that ETFDH (P =  0.047) was an independent predictor of overall survival. Our findings may shed new light on the identification of new prognostic marker for HCC.