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Erschienen in: Tumor Biology 6/2011

01.12.2011 | Research Article

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

verfasst von: Can-Liang Lu, Ji-Liang Qiu, Pin-Zhu Huang, Ru-Hai Zou, Jian Hong, Bin-Kui Li, Gui-Hua Chen, Yun-Fei Yuan

Erschienen in: Tumor Biology | Ausgabe 6/2011

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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.
Literatur
1.
Zurück zum Zitat Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.PubMedCrossRef Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.PubMedCrossRef
2.
Zurück zum Zitat El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132:2557–76.PubMedCrossRef El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132:2557–76.PubMedCrossRef
3.
Zurück zum Zitat Altekruse SF, McGlynn KA, Reichman ME. Hepatocellular carcinoma incidence, mortality, and survival trends in the united states from 1975 to 2005. J Clin Oncol. 2009;27:1485–91.PubMedCrossRef Altekruse SF, McGlynn KA, Reichman ME. Hepatocellular carcinoma incidence, mortality, and survival trends in the united states from 1975 to 2005. J Clin Oncol. 2009;27:1485–91.PubMedCrossRef
4.
Zurück zum Zitat Befeler AS, Di Bisceglie AM. Hepatocellular carcinoma: diagnosis and treatment. Gastroenterology. 2002;122:1609–19.PubMedCrossRef Befeler AS, Di Bisceglie AM. Hepatocellular carcinoma: diagnosis and treatment. Gastroenterology. 2002;122:1609–19.PubMedCrossRef
5.
Zurück zum Zitat Trachootham D, Alexandre J, Huang P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov. 2009;8:579–91.PubMedCrossRef Trachootham D, Alexandre J, Huang P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov. 2009;8:579–91.PubMedCrossRef
6.
Zurück zum Zitat Diehn M, Cho RW, Lobo NA, Kalisky T, Dorie MJ, Kulp AN, et al. Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature. 2009;458:780–3.PubMedCrossRef Diehn M, Cho RW, Lobo NA, Kalisky T, Dorie MJ, Kulp AN, et al. Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature. 2009;458:780–3.PubMedCrossRef
7.
Zurück zum Zitat Brown DI, Griendling KK. Nox proteins in signal transduction. Free Radic Biol Med. 2009;47:1239–53.PubMedCrossRef Brown DI, Griendling KK. Nox proteins in signal transduction. Free Radic Biol Med. 2009;47:1239–53.PubMedCrossRef
8.
Zurück zum Zitat Nauseef WM. Biological roles for the NOX family NADPH oxidases. J Biol Chem. 2008;283:16961–5.PubMedCrossRef Nauseef WM. Biological roles for the NOX family NADPH oxidases. J Biol Chem. 2008;283:16961–5.PubMedCrossRef
9.
Zurück zum Zitat Paik YH, Iwaisako K, Seki E, Inokuchi S, Schnabl B, Osterreicher CH, et al. The nicotinamide adenine dinucleotide phosphate oxidase homologues NOX1 and NOX2/gp91phox mediate hepatic fibrosis in mice. Hepatology. 2011;53:1730–41.PubMedCrossRef Paik YH, Iwaisako K, Seki E, Inokuchi S, Schnabl B, Osterreicher CH, et al. The nicotinamide adenine dinucleotide phosphate oxidase homologues NOX1 and NOX2/gp91phox mediate hepatic fibrosis in mice. Hepatology. 2011;53:1730–41.PubMedCrossRef
10.
Zurück zum Zitat Ishikawa K, Takenaga K, Akimoto M, Koshikawa N, Yamaguchi A, Imanishi H, et al. Ros-generating mitochondrial DNA mutations can regulate tumor cell metastasis. Science. 2008;320:661–4.PubMedCrossRef Ishikawa K, Takenaga K, Akimoto M, Koshikawa N, Yamaguchi A, Imanishi H, et al. Ros-generating mitochondrial DNA mutations can regulate tumor cell metastasis. Science. 2008;320:661–4.PubMedCrossRef
11.
Zurück zum Zitat Garrido-Urbani S, Jemelin S, Deffert C, Carnesecchi S, Basset O, Szyndralewiez C, et al. Targeting vascular NADPH oxidase 1 blocks tumor angiogenesis through a PPARalpha mediated mechanism. PLoS One. 2011;6:e14665.PubMedCrossRef Garrido-Urbani S, Jemelin S, Deffert C, Carnesecchi S, Basset O, Szyndralewiez C, et al. Targeting vascular NADPH oxidase 1 blocks tumor angiogenesis through a PPARalpha mediated mechanism. PLoS One. 2011;6:e14665.PubMedCrossRef
12.
Zurück zum Zitat Schumacker PT. SIRT3 controls cancer metabolic reprogramming by regulating ROS and HIF. Cancer Cell. 2011;19:299–300.PubMedCrossRef Schumacker PT. SIRT3 controls cancer metabolic reprogramming by regulating ROS and HIF. Cancer Cell. 2011;19:299–300.PubMedCrossRef
13.
Zurück zum Zitat Ushio-Fukai M, Nakamura Y. Reactive oxygen species and angiogenesis: NADPH oxidase as target for cancer therapy. Cancer Lett. 2008;266:37–52.PubMedCrossRef Ushio-Fukai M, Nakamura Y. Reactive oxygen species and angiogenesis: NADPH oxidase as target for cancer therapy. Cancer Lett. 2008;266:37–52.PubMedCrossRef
14.
Zurück zum Zitat Lee JK, Edderkaoui M, Truong P, Ohno I, Jang KT, Berti A, et al. NADPH oxidase promotes pancreatic cancer cell survival via inhibiting JAK2 dephosphorylation by tyrosine phosphatases. Gastroenterology. 2007;133:1637–48.PubMedCrossRef Lee JK, Edderkaoui M, Truong P, Ohno I, Jang KT, Berti A, et al. NADPH oxidase promotes pancreatic cancer cell survival via inhibiting JAK2 dephosphorylation by tyrosine phosphatases. Gastroenterology. 2007;133:1637–48.PubMedCrossRef
15.
Zurück zum Zitat Maranchie JK, Zhan Y. Nox4 is critical for hypoxia-inducible factor 2-alpha transcriptional activity in von Hippel–Lindau-deficient renal cell carcinoma. Cancer Res. 2005;65:9190–3.PubMedCrossRef Maranchie JK, Zhan Y. Nox4 is critical for hypoxia-inducible factor 2-alpha transcriptional activity in von Hippel–Lindau-deficient renal cell carcinoma. Cancer Res. 2005;65:9190–3.PubMedCrossRef
16.
Zurück zum Zitat Kumar B, Koul S, Khandrika L, Meacham RB, Koul HK. Oxidative stress is inherent in prostate cancer cells and is required for aggressive phenotype. Cancer Res. 2008;68:1777–85.PubMedCrossRef Kumar B, Koul S, Khandrika L, Meacham RB, Koul HK. Oxidative stress is inherent in prostate cancer cells and is required for aggressive phenotype. Cancer Res. 2008;68:1777–85.PubMedCrossRef
17.
Zurück zum Zitat Yamaura M, Mitsushita J, Furuta S, Kiniwa Y, Ashida A, Goto Y, et al. NADPH oxidase 4 contributes to transformation phenotype of melanoma cells by regulating G2-M cell cycle progression. Cancer Res. 2009;69:2647–54.PubMedCrossRef Yamaura M, Mitsushita J, Furuta S, Kiniwa Y, Ashida A, Goto Y, et al. NADPH oxidase 4 contributes to transformation phenotype of melanoma cells by regulating G2-M cell cycle progression. Cancer Res. 2009;69:2647–54.PubMedCrossRef
18.
Zurück zum Zitat Moon EJ, Sonveaux P, Porporato PE, Danhier P, Gallez B, Batinic-Haberle I, et al. NADPH oxidase-mediated reactive oxygen species production activates hypoxia-inducible factor-1 (HIF-1) via the ERK pathway after hyperthermia treatment. Proc Natl Acad Sci U S A. 2010;107:20477–82.PubMedCrossRef Moon EJ, Sonveaux P, Porporato PE, Danhier P, Gallez B, Batinic-Haberle I, et al. NADPH oxidase-mediated reactive oxygen species production activates hypoxia-inducible factor-1 (HIF-1) via the ERK pathway after hyperthermia treatment. Proc Natl Acad Sci U S A. 2010;107:20477–82.PubMedCrossRef
19.
Zurück zum Zitat Xia C, Meng Q, Liu LZ, Rojanasakul Y, Wang XR, Jiang BH. Reactive oxygen species regulate angiogenesis and tumor growth through vascular endothelial growth factor. Cancer Res. 2007;67:10823–30.PubMedCrossRef Xia C, Meng Q, Liu LZ, Rojanasakul Y, Wang XR, Jiang BH. Reactive oxygen species regulate angiogenesis and tumor growth through vascular endothelial growth factor. Cancer Res. 2007;67:10823–30.PubMedCrossRef
20.
Zurück zum Zitat Pulcrano M, Boukheris H, Talbot M, Caillou B, Dupuy C, Virion A, et al. Poorly differentiated follicular thyroid carcinoma: prognostic factors and relevance of histological classification. Thyroid. 2007;17:639–46.PubMedCrossRef Pulcrano M, Boukheris H, Talbot M, Caillou B, Dupuy C, Virion A, et al. Poorly differentiated follicular thyroid carcinoma: prognostic factors and relevance of histological classification. Thyroid. 2007;17:639–46.PubMedCrossRef
21.
Zurück zum Zitat Luxen S, Belinsky SA, Knaus UG. Silencing of DUOX NADPH oxidases by promoter hypermethylation in lung cancer. Cancer Res. 2008;68:1037–45.PubMedCrossRef Luxen S, Belinsky SA, Knaus UG. Silencing of DUOX NADPH oxidases by promoter hypermethylation in lung cancer. Cancer Res. 2008;68:1037–45.PubMedCrossRef
22.
Zurück zum Zitat Huang P, Qiu J, Li B, Hong J, Lu C, Wang L, et al. Role of Sox2 and Oct4 in predicting survival of hepatocellular carcinoma patients after hepatectomy. Clin Biochem. 2011;44:582–9.PubMedCrossRef Huang P, Qiu J, Li B, Hong J, Lu C, Wang L, et al. Role of Sox2 and Oct4 in predicting survival of hepatocellular carcinoma patients after hepatectomy. Clin Biochem. 2011;44:582–9.PubMedCrossRef
23.
Zurück zum Zitat Tian J, Tang ZY, Ye SL, Liu YK, Lin ZY, Chen J, et al. New human hepatocellular carcinoma (HCC) cell line with highly metastatic potential (MHCC97) and its expressions of the factors associated with metastasis. Br J Cancer. 1999;81:814–21.PubMedCrossRef Tian J, Tang ZY, Ye SL, Liu YK, Lin ZY, Chen J, et al. New human hepatocellular carcinoma (HCC) cell line with highly metastatic potential (MHCC97) and its expressions of the factors associated with metastasis. Br J Cancer. 1999;81:814–21.PubMedCrossRef
24.
Zurück zum Zitat Mochizuki T, Furuta S, Mitsushita J, Shang WH, Ito M, Yokoo Y, et al. Inhibition of NADPH oxidase 4 activates apoptosis via the AKT/apoptosis signal-regulating kinase 1 pathway in pancreatic cancer PANC-1 cells. Oncogene. 2006;25:3699–707.PubMedCrossRef Mochizuki T, Furuta S, Mitsushita J, Shang WH, Ito M, Yokoo Y, et al. Inhibition of NADPH oxidase 4 activates apoptosis via the AKT/apoptosis signal-regulating kinase 1 pathway in pancreatic cancer PANC-1 cells. Oncogene. 2006;25:3699–707.PubMedCrossRef
25.
Zurück zum Zitat Lu SN, Wang JH, Liu SL, Hung CH, Chen CH, Tung HD, et al. Thrombocytopenia as a surrogate for cirrhosis and a marker for the identification of patients at high-risk for hepatocellular carcinoma. Cancer. 2006;107:2212–22.PubMedCrossRef Lu SN, Wang JH, Liu SL, Hung CH, Chen CH, Tung HD, et al. Thrombocytopenia as a surrogate for cirrhosis and a marker for the identification of patients at high-risk for hepatocellular carcinoma. Cancer. 2006;107:2212–22.PubMedCrossRef
26.
Zurück zum Zitat Belghiti J. Resection and liver transplantation for HCC. J Gastroenterol. 2009;44 Suppl 19:132–5.PubMedCrossRef Belghiti J. Resection and liver transplantation for HCC. J Gastroenterol. 2009;44 Suppl 19:132–5.PubMedCrossRef
27.
Zurück zum Zitat Bedard K, Krause KH. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev. 2007;87:245–313.PubMedCrossRef Bedard K, Krause KH. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev. 2007;87:245–313.PubMedCrossRef
Metadaten
Titel
NADPH oxidase DUOX1 and DUOX2 but not NOX4 are independent predictors in hepatocellular carcinoma after hepatectomy
verfasst von
Can-Liang Lu
Ji-Liang Qiu
Pin-Zhu Huang
Ru-Hai Zou
Jian Hong
Bin-Kui Li
Gui-Hua Chen
Yun-Fei Yuan
Publikationsdatum
01.12.2011
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 6/2011
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-011-0220-3

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