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Diagnostic and prognostic significance of peroxiredoxin 1 expression in human hepatocellular carcinoma

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Abstract

Peroxiredoxin 1 (Prdx1) is a member of the peroxiredoxin family of antioxidant enzymes and implicated in cell differentiation, proliferation, and apoptosis. The aim of the present study was to determine the expression and diagnostic and prognostic significance of Prdx1 in human hepatocellular carcinoma (HCC). Prdx1 expression was examined in 76 HCC patients and 20 healthy volunteers. The relationships between Prdx1 expression and clinicopathological features were analyzed. Receiver operating characteristics analysis was used to calculate the diagnostic accuracy of serum Prdx1, serum alpha-fetoprotein (AFP), and their combination. The prognostic impact of Prdx1 on overall survival (OS) and disease-free survival (DFS) of HCC patients was investigated. Prdx1-positive rate was significantly (p < 0.05) higher in HCC (77.1 %) than in adjacent non-tumorous liver tissues (18.4 %). Prdx1 immunoreactivity was positively correlated with tumor vascular endothelial growth factor expression and microvessel density. Prdx1 expression was significantly associated with tumor size, microvascular invasion, Edmondson grade, tumor capsula status, serum AFP, and tumor-node-metastasis stage. The combination of serum Prdx1 and AFP had a markedly higher area under the curve than serum Prdx1 alone. Positive Prdx1 expression was associated with unfavorable OS (p = 0.004) and DFS (p = 0.001). Multivariate analysis revealed intra-tumoral Prdx1 staining as an independent poor prognostic marker for OS (p = 0.006) and DFS (p = 0.002). Taken together, our data suggest that increased Prdx1 expression is associated with tumor angiogenesis and progression in HCC and serves as a promising biomarker for detection and prognosis of this malignancy.

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Abbreviations

AFP:

α-Fetoprotein

DAB:

3,3-Diaminobenzidine tetrahydrochloride

DFS:

Disease-free survival

ELISA:

Enzyme-linked immunosorbent assay

EMT:

Epithelial-mesenchymal transition

HBeAg:

Hepatitis B e antigen

HCC:

Hepatocellular carcinoma

HE:

Hematoxylin and eosin

MVD:

Microvessel density

OS:

Overall survival

PBS:

Phosphate buffered saline

Prdx1:

Peroxiredoxin 1

ROC:

Receiver operating characteristics

SD:

Standard deviation

TLR4:

Toll-like receptor 4

TNM:

Tumor-node-metastasis

TRAIL:

Tumor necrosis factor-related apoptosis-inducing ligand

VEGF:

Vascular endothelial growth factor

References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.

    Article  PubMed  Google Scholar 

  2. 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.

    Article  PubMed  Google Scholar 

  3. El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365:1118–27.

    Article  CAS  PubMed  Google Scholar 

  4. Wood ZA, Schroder E, Robin Harris J, Poole LB. Structure, mechanism and regulation of peroxiredoxins. Trends Biochem Sci. 2003;28:32–40.

    Article  CAS  PubMed  Google Scholar 

  5. Kim JH, Lee JM, Lee HN, Kim EK, Ha B, Ahn SM, et al. RNA-binding properties and RNA chaperone activity of human peroxiredoxin 1. Biochem Biophys Res Commun. 2012;425:730–4.

    Article  CAS  PubMed  Google Scholar 

  6. Yanagawa T, Ishikawa T, Ishii T, Tabuchi K, Iwasa S, Bannai S, et al. Peroxiredoxin I expression in human thyroid tumors. Cancer Lett. 1999;145:127–32.

    Article  CAS  PubMed  Google Scholar 

  7. Quan C, Cha EJ, Lee HL, Han KH, Lee KM, Kim WJ. Enhanced expression of peroxiredoxin I and VI correlates with development, recurrence and progression of human bladder cancer. J Urol. 2006;175:1512–6.

    Article  CAS  PubMed  Google Scholar 

  8. Kim JH, Bogner PN, Baek SH, Ramnath N, Liang P, Kim HR, et al. Up-regulation of peroxiredoxin 1 in lung cancer and its implication as a prognostic and therapeutic target. Clin Cancer Res. 2008;14:2326–33.

    Article  CAS  PubMed  Google Scholar 

  9. Riddell JR, Bshara W, Moser MT, Spernyak JA, Foster BA, Gollnick SO. Peroxiredoxin 1 controls prostate cancer growth through toll-like receptor 4-dependent regulation of tumor vasculature. Cancer Res. 2011;71:1637–46.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Neumann CA, Krause DS, Carman CV, Das S, Dubey DP, Abraham JL. Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression. Nature. 2003;424:561–5.

    Article  CAS  PubMed  Google Scholar 

  11. Hoshino I, Matsubara H, Hanari N, Mori M, Nishimori T, Yoneyama Y, et al. Histone deacetylase inhibitor FK228 activates tumor suppressor Prdx1 with apoptosis induction in esophageal cancer cells. Clin Cancer Res. 2005;11:7945–52.

    Article  CAS  PubMed  Google Scholar 

  12. Song IS, Kim SU, Oh NS, Kim J, Yu DY, Huang SM, et al. Peroxiredoxin I contributes to TRAIL resistance through suppression of redox-sensitive caspase activation in human hepatoma cells. Carcinogenesis. 2009;30:1106–14.

    Article  CAS  PubMed  Google Scholar 

  13. Edmondson HA, Steiner PE. Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer. 1954;7:462–503.

    Article  CAS  PubMed  Google Scholar 

  14. Shao R, Bao S, Bai X, Blanchette C, Anderson RM, Dang T, et al. Acquired expression of periostin by human breast cancers promotes tumor angiogenesis through up-regulation of vascular endothelial growth factor receptor 2 expression. Mol Cell Biol. 2004;24:3992–4003.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Bertino G, Ardiri A, Malaguarnera M, Malaguarnera G, Bertino N, Calvagno GS. Hepatocellualar carcinoma serum markers. Semin Oncol. 2012;39:410–33.

    Article  CAS  PubMed  Google Scholar 

  16. Qiao B, Wang J, Xie J, Niu Y, Ye S, Wan Q, et al. Detection and identification of peroxiredoxin 3 as a biomarker in hepatocellular carcinoma by a proteomic approach. Int J Mol Med. 2012;29:832–40.

    CAS  PubMed  Google Scholar 

  17. Rostila A, Puustinen A, Toljamo T, Vuopala K, Lindström I, Nyman TA, et al. Peroxiredoxins and tropomyosins as plasma biomarkers for lung cancer and asbestos exposure. Lung Cancer. 2012;77:450–9.

    Article  PubMed  Google Scholar 

  18. Du ZX, Yan Y, Zhang HY, Liu BQ, Gao YY, Niu XF, et al. Suppression of MG132-mediated cell death by peroxiredoxin 1 through influence on ASK1 activation in human thyroid cancer cells. Endocr Relat Cancer. 2010;17:553–60.

    Article  CAS  PubMed  Google Scholar 

  19. Ha B, Kim EK, Kim JH, Lee HN, Lee KO, Lee SY, et al. Human peroxiredoxin 1 modulates TGF-β1-induced epithelial-mesenchymal transition through its peroxidase activity. Biochem Biophys Res Commun. 2012;421:33–7.

    Article  CAS  PubMed  Google Scholar 

  20. Lee TK, Poon RT, Yuen AP, Ling MT, Kwok WK, Wang XH, et al. Twist overexpression correlates with hepatocellular carcinoma metastasis through induction of epithelial-mesenchymal transition. Clin Cancer Res. 2006;12:5369–76.

    Article  CAS  PubMed  Google Scholar 

  21. Folkman J. Role of angiogenesis in tumor growth and metastasis. Semin Oncol. 2002;29:15–8.

    CAS  PubMed  Google Scholar 

  22. Chen ZB, Shen SQ, Ding YM, Wang WX, Tao JP, Liang LJ, et al. The angiogenic and prognostic implications of VEGF, Ang-1, Ang-2, and MMP-9 for hepatocellular carcinoma with background of hepatitis B virus. Med Oncol. 2009;26:365–71.

    Article  CAS  PubMed  Google Scholar 

  23. Wada H, Nagano H, Yamamoto H, Yang Y, Kondo M, Ota H, et al. Expression pattern of angiogenic factors and prognosis after hepatic resection in hepatocellular carcinoma: importance of angiopoietin-2 and hypoxia-induced factor-1 alpha. Liver Int. 2006;26:414–23.

    Article  CAS  PubMed  Google Scholar 

  24. Riddell JR, Maier P, Sass SN, Moser MT, Foster BA, Gollnick SO. Peroxiredoxin 1 stimulates endothelial cell expression of VEGF via TLR4 dependent activation of HIF-1α. PLoS ONE. 2012;7:e50394.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Kim JH, Bogner PN, Ramnath N, Park Y, Yu J, Park YM. Elevated peroxiredoxin 1, but not NF-E2-related factor 2, is an independent prognostic factor for disease recurrence and reduced survival in stage I non-small cell lung cancer. Clin Cancer Res. 2007;13:3875–82.

    Article  CAS  PubMed  Google Scholar 

  26. Yonglitthipagon P, Pairojkul C, Chamgramol Y, Loukas A, Mulvenna J, Bethony J, et al. Prognostic significance of peroxiredoxin 1 and ezrin–radixin–moesin—binding phosphoprotein 50 in cholangiocarcinoma. Hum Pathol. 2012;43:1719–30.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Li J, Yang ZL, Ren X, Zou Q, Yuan Y, Liang L, et al. ILK and PRDX1 are prognostic markers in squamous cell/adenosquamous carcinomas and adenocarcinoma of gallbladder. Tumour Biol. 2013;34:359–68.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This research was supported by the National Natural Science Foundation of China (Nos. 81201906 and 81172364).

Conflict of interest

The authors declare no competing financial interests.

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Authors and Affiliations

  1. Department of Hepatic Surgery, Anhui Provincial Hospital, Anhui Medical University, Hefei, 230001, People’s Republic of China

    Qi-Kai Sun, Jian-Yu Zhu, Yang Lv, Ji-Hai Yu, Ge-Liang Xu, Jin-Liang Ma & Wei-Dong Jia

  2. Department of Medical Oncology, Anhui Provincial Hospital, Anhui Medical University, No. 17 Lujiang Road, Hefei, 230001, People’s Republic of China

    Wei Wang

  3. Department of Pathology, Anhui Provincial Hospital, Anhui Medical University, Hefei, 230001, People’s Republic of China

    Hang-Cheng Zhou & Wen Zhong

  4. Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, No. 17 Lujiang Road, Hefei, 230001, People’s Republic of China

    Ge-Liang Xu & Wei-Dong Jia

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  1. Qi-Kai Sun
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  2. Jian-Yu Zhu
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  3. Wei Wang
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Corresponding authors

Correspondence to Wei Wang or Wei-Dong Jia.

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Qi-Kai Sun and Jian-Yu Zhu have contributed equally to this work as co-first authors.

Wei Wang and Wei-Dong Jia have contributed equally to this work as co-correspondence authors.

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Sun, QK., Zhu, JY., Wang, W. et al. Diagnostic and prognostic significance of peroxiredoxin 1 expression in human hepatocellular carcinoma. Med Oncol 31, 786 (2014). https://doi.org/10.1007/s12032-013-0786-2

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  • DOI: https://doi.org/10.1007/s12032-013-0786-2

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