NADPH oxidase DUOX1 and DUOX2 but not NOX4 are independent predictors in hepatocellular carcinoma after hepatectomy.

NADPH oxidase DUOX1, DUOX2, and NOX4 have recently been gained considerable concerns, owing to the fact that they involve in reactive oxygen species-induced genetic and epigenetic alternations of human carcinogenesis and serve as biomarkers in several cancers. Whether they predict survival in hepatocellular carcinoma (HCC) is still uncertain. Here, we detected the expressions of DUOX1, DUOX2, and NOX4 in one normal liver cell line, seven HCC cell lines, 30 non-cirrhotic normal liver tissues, and 107 paired HCC tissues using reverse transcription-polymerase chain reaction. The correlations of genes expression with prognoses were analyzed. DUOX1 was expressed at high levels in MHCC-97H and MHCC-97L, but at low levels in Bel-7402. In contrast to low expression level at SMMC-7721, DUOX2 was expressed at considerably high levels in MHCC-97H and MHCC-97L. The transcript of NOX4 was only detected in SMMC-7721. All the 30 normal liver tissues failed to express the three candidate markers. Compared with adjacent non-neoplastic tissues, DUOX1, DUOX2, and NOX4 were expressed at higher frequencies in tumor specimens. Both univariate and multivariate analyses revealed that elevated expression of DUOX1 or DUOX2 predicted poorer recurrence-free survival and overall survival. No such significance trend regarding NOX4 predictive value in survival, however, was seen in univariate analysis. These results suggested DUOX1 and DUOX2, but not NOX4, could predict HCC prognoses after hepatectomy.

[OCT4 expression in hepatocellular carcinoma and its clinical significance].

BACKGROUND AND OBJECTIVE: Recently, many studies have focused on stem cells in hepatocellular carcinoma (HCC) and found some stem cell markers in HCC, which are associated with the prognosis. OCT4, as a member of the POU transcription factor family, is a key factor to maintain self-renewal and pluripotency of embryonic stem cells (ESCs). This study was to explore the expression of the ESCs marker OCT4A in HCC, and its correlations with clinicopathologic features and prognosis of HCC. METHODS: OCT4A mRNA expression was detected in five liver cancer cell lines (SMMC-7721, BEL-7402, Hep-G2, MHCC97-L, and MHCC97-H), one immortalized liver cell line L-O2, tumor tissues with matched non-neoplastic liver tissues in 107 HCC patients, and normal liver tissues of 20 cases using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). The correlations between OCT4A mRNA and clinicopathologic features and prognosis of HCC were analyzed. RESULTS: OCT4A mRNA was detected in SMMC-7721, BEL-7402, Hep-G2, MHCC-97L, and MHCC-97H cells, but not in L-O2 cells. The positive rate of OCT4A mRNA expression was significantly higher in the HCC tissues than in the non-neoplastic liver tissues (72.0% vs. 30.8%, P<0.001). No OCT4A mRNA expression was found in the normal liver tissues. OCT4A mRNA expression was correlated with the tumor size, vascular invasion, and TNM stage (P<0.05). Kaplan-Meier survival curves showed that patients with positive expression of OCT4A mRNA had lower overall survival and disease-free survival rates. CONCLUSIONS: OCT4A mRNA, which is highly expressed in a subset of liver cancer cell lines and HCC tissues, may be involved in the carcinogenesis of HCC. OCT4A mRNA may be a valuable biomarker for assessing the prognosis of HCC.