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

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Tumor Biology

Abstract

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.

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Abbreviations

HCC:

Hepatocellular carcinoma

RT–PCR:

Reverse transcription–polymerase chain reaction

ROS:

Reactive oxygen species

DUOX :

Dual oxidase

NOX4 :

NADPH oxidase 4

GGT:

Gamma-glutamyltransferase

AFP:

α-Fetoprotein

HBsAg:

Hepatitis B surface antigen

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (30872489 and 30972916). The authors thank all the patients who participated in this study.

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Authors and Affiliations

  1. State Key Laboratory of Oncology in South China and Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, China

    Can-Liang Lu, Ji-Liang Qiu, Pin-Zhu Huang, Ru-Hai Zou, Jian Hong, Bin-Kui Li & Yun-Fei Yuan

  2. Department of General Surgery, Beijing Shijitan Hospital, Beijing, 100038, China

    Can-Liang Lu

  3. Department of Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510630, China

    Gui-Hua Chen

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  1. Can-Liang Lu
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Corresponding author

Correspondence to Yun-Fei Yuan.

Additional information

Can-Liang Lu and Ji-Liang Qiu contributed equally to this work.

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Lu, CL., Qiu, JL., Huang, PZ. et al. NADPH oxidase DUOX1 and DUOX2 but not NOX4 are independent predictors in hepatocellular carcinoma after hepatectomy. Tumor Biol. 32, 1173–1182 (2011). https://doi.org/10.1007/s13277-011-0220-3

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  • DOI: https://doi.org/10.1007/s13277-011-0220-3

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