DOI QR코드

DOI QR Code

Serum Peroxiredoxin3 is a Useful Biomarker for Early Diagnosis and Assessemnt of Prognosis of Hepatocellular Carcinoma in Chinese Patients

  • Shi, Liang (Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University) ;
  • Wu, Li-Li (Wenzhou Medical University) ;
  • Yang, Jian-Rong (Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University) ;
  • Chen, Xiao-Fei (Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University) ;
  • Zhang, Yi (Department of liver and gall Surgery, The First Affiliated Hospital of Wenzhou Medical University) ;
  • Chen, Zeng-Qiang (Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University) ;
  • Liu, Cun-Li (Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University) ;
  • Chi, Sheng-Ying (Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University) ;
  • Zheng, Jia-Ying (Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University) ;
  • Huang, Hai-Xia (Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University) ;
  • Yu, Fu-Jun (Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University) ;
  • Lin, Xiang-Yang (Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University)
  • Published : 2014.04.01

Abstract

Background: Recently, peroxiredoxin3 (PRDX3) was identified as a novel molecular marker for the progression of hepatocellular carcinoma (HCC). However, its potential clinical application as a serum marker for the early diagnosis and prognosis of HCC has not been investigated. Methods: PRDX3, alpha-fetaprotein (AFP), and other biochemical parameters were measured in serum samples from 297 Chinese patients, including 96 with HCC, 98 with liver cirrhosis (LC), and 103 healthy controls (HCs). Correlations between serum PRDX3 expression and clinicopathological variables and the relationship between serum PRDX3 expression and prognosis were analyzed. Results: Serum PRDX3 was significantly higher in HCC patients than in the LC and HC groups. The sensitivity and specificity of serum PRDX3 for the diagnosis of HCC were 85.9% and 75.3%, respectively, at a cutoff of 153.26 ng/mL, and the area under the curve was 0.865. Moreover, serum PRDX3 expression was strongly associated with AFP level, tumor diameter, TNM stage, and portal vein invasion. Kaplan-Meier curve analysis revealed that HCC patients with high serum PRDX3 expression had a shorter median survival time than those with low PRDX3 expression. Moreover, serum PRDX3 expression was an independent risk factor for overall survival. The inverse correlation between serum PRDX3 and patient survival remained significant in patients with early-stage HCC and in those with normal serum AFP levels. Conclusions: Serum PRDX3 can be used as a noninvasive biomarker for the diagnosis and/or prognosis of HCC.

Keywords

Alpha-fetoprotein;peroxiredoxin3;hepatocellular carcinoma;biomarker

References

  1. Song IS, Kim HK, Jeong SH, et al (2011). Mitochondrial peroxiredoxin III is a potential target for cancer therapy. Int J Mol Sci, 12, 7163-85 https://doi.org/10.3390/ijms12107163
  2. Rabilloud T, Heller M, Gasnier F, et al (2002). Proteomics analysis of cellular response to oxidative stress. Evidence for in vivo overoxidation of peroxiredoxins at their active site. J Biol Chem, 277, 19396-401. https://doi.org/10.1074/jbc.M106585200
  3. Shariff MI, Cox IJ, Gomaa AI, et al (2009). Hepatocellular carcinoma: current trends in worldwide epidemiology, risk factors, diagnosis and therapeutics. Expert Rev Gastroenterol Hepatol, 3, 353-67. https://doi.org/10.1586/egh.09.35
  4. Shen Q, Fan J, Yang XR, et al (2012). Serum DKK1 as a protein biomarker for the diagnosis of hepatocellular carcinoma: a large-scale, multicentre study. Lancet Oncol, 13, 817-26. https://doi.org/10.1016/S1470-2045(12)70233-4
  5. Trachootham D, Alexandre J, Huang P. (2009). Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov, 8, 579-91. https://doi.org/10.1038/nrd2803
  6. Wonsey DR, Zeller KI, Dang CV (2002). The c-Myc target gene PRDX3 is required for mitochondrial homeostasis and neoplastic transformation. Proc Natl Acad Sci USA, 99, 6649-54. https://doi.org/10.1073/pnas.102523299
  7. Wu XY, Fu ZX, Wang XH (2010). Peroxiredoxins in colorectal neoplasms. Histol Histopathol, 25, 1297-303.
  8. Yamamoto K, Imamura H, Matsuyama Y, et al (2010). AFP, AFP-L3, DCP, and GP73 as markers for monitoring treatment response and recurrence and as surrogate markers of clinicopathological variables of HCC. J Gastroenterol, 45, 1272-82. https://doi.org/10.1007/s00535-010-0278-5
  9. Liu L, Zhang CZ, Cai M, et al (2012). Downregulation of polo-like kinase 4 in hepatocellular carcinoma associates with poor prognosis. PLoS One, 7, 41293. https://doi.org/10.1371/journal.pone.0041293
  10. Kim K, Yu M, Han S, et al (2009). Expression of human peroxiredoxin isoforms in response to cervical carcinogenesis. Oncol Rep, 21, 1391-96.
  11. Kudo M. (2010) Management of hepatocellular carcinoma: from prevention to molecular targeted therapy. Oncology, 78, 1-6.
  12. Li XQ, Zhang SL, Cai Z, et al (2009). Proteomic identification of tumor-associated protein in ovarian serous cystadenocarinoma. Cancer Lett, 275, 109-16. https://doi.org/10.1016/j.canlet.2008.10.019
  13. Liu X, Feng R, Du L (2010). The role of enoyl-CoA hydratase short chain 1 and peroxiredoxin 3 in PP2-induced apoptosis in human breast cancer MCF-7 cells. FEBS Lett, 584, 3185-92. https://doi.org/10.1016/j.febslet.2010.06.002
  14. Mao Y, Yang H, Xu H, et al (2010). Golgi protein 73 (GOLPH2) is a valuable serum marker for hepatocellular carcinoma. Gut, 59, 1687-93. https://doi.org/10.1136/gut.2010.214916
  15. Marquardt JU, Galle PR, Teufel A (2012). [Hepatocellular carcinoma: molecular pathogenesis and novel targets for therapy]. Dtsch Med Wochenschr, 137, 855-60. https://doi.org/10.1055/s-0032-1304843
  16. Marra M, Sordelli IM, Lombardi A, et al (2011). Molecular targets and oxidative stress biomarkers in hepatocellular carcinoma: an overview. J Transl Med, 9, 171. https://doi.org/10.1186/1479-5876-9-171
  17. Nagasue N (1998). Liver resection for hepatocellular carcinoma: indications, techniques, complications, and prognostic factors. J Hepatobiliary Pancreat Surg, 5, 7-13. https://doi.org/10.1007/PL00009954
  18. Pateron D, Ganne N, Trinchet JC, et al (1994). Prospective study of screening for hepatocellular carcinoma in Caucasian patients with cirrhosis. J Hepatol, 20, 65-71. https://doi.org/10.1016/S0168-8278(05)80468-4
  19. Qiao B, Wang J, Xie J, et al (2012). Detection and identification of by a proteomic approach. Int J Mol Med, 29, 832-40.
  20. Dietz KJ, Horling F, Konig J, Baier M (2002). The function of oroplast 2-cysteine peroxiredoxin in peroxide detoxification and its regulation. J Exp Bot, 53, 1321-29. https://doi.org/10.1093/jexbot/53.372.1321
  21. Basu A, Banerjee H, Rojas H, et al (2011). Differential expression of peroxiredoxins in prostate cancer: consistent upregulation of PRDX3 and PRDX4. Prostate, 71, 755-65. https://doi.org/10.1002/pros.21292
  22. Breuhahn K, Gores G, Schirmacher P (2011). Strategies for hepatocellular carcinoma therapy and diagnostics: lessons learned from high throughput and profiling approaches. Hepatology, 53, 2112-21. https://doi.org/10.1002/hep.24313
  23. Dai Z, Yin J, He H, et al (2010). Mitochondrial comparative proteomics of human ovarian cancer cells and their platinum-resistant sublines. Proteomics, 10, 3789-99. https://doi.org/10.1002/pmic.200900685
  24. Fu J, Qiu H, Cai M, et al (2013). Low cyclin F expression in hepatocellular carcinoma associates with poor differentiation and unfavorable prognosis. Cancer Sci, 104, 508-15. https://doi.org/10.1111/cas.12100
  25. Huang HC, Zheng S, VanBuren V, Zhao Z (2009). Discovering disease-specific biomarker genes for cancer diagnosis and prognosis. Technol Cancer Res Treat, 9, 219-30.
  26. Huh JY, Kim Y, Jeong J, et al (2012). Peroxiredoxin 3 is a key molecule regulating adipocyte oxidative stress, mitochondrial biogenesis, and adipokine expression. Antioxid Redox Signal, 16, 229-43. https://doi.org/10.1089/ars.2010.3766
  27. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
  28. Ji D, Lu ZT, Li YQ, et al (2014) MACC1 expression correlates with pfkfb2 and survival in hepatocellular carcinoma. Asian Pac J Cancer Prev, 15, 999-100 https://doi.org/10.7314/APJCP.2014.15.2.999
  29. Jo M, Nishikawa T, Nakajima T, et al (2011). Oxidative stress is closely associated with tumor angiogenesis of hepatocellular carcinoma. J Gastroentero, 46, 809-21. https://doi.org/10.1007/s00535-011-0392-z
  30. Altekruse SF, McGlynn KA, Reichman ME (2009). Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol, 27, 1485-91. https://doi.org/10.1200/JCO.2008.20.7753

Cited by

  1. Differential Expression of IQGAP1/2 in Hepatocellular Carcinoma and its Relationship with Clinical Outcomes vol.15, pp.12, 2014, https://doi.org/10.7314/APJCP.2014.15.12.4951
  2. Elevated PIVKA-II is Associated with Early Recurrence and Poor Prognosis in BCLC 0-A Hepatocellular Carcinomas vol.15, pp.16, 2014, https://doi.org/10.7314/APJCP.2014.15.16.6673
  3. Plasma Nuclear Factor Kappa B and Serum Peroxiredoxin 3 in Early Diagnosis of Hepatocellular Carcinoma vol.16, pp.4, 2015, https://doi.org/10.7314/APJCP.2015.16.4.1657
  4. Inhibits Growth and Promotes Invasion and Extracellular Matrix Degradation in Hepatocellular Carcinoma Cells vol.15, pp.5, 2016, https://doi.org/10.1021/acs.jproteome.5b01125
  5. Accuracy of novel diagnostic biomarkers for hepatocellular carcinoma: An update for clinicians (Review) vol.36, pp.2, 2016, https://doi.org/10.3892/or.2016.4842
  6. Epigenetic regulation of peroxiredoxins: Implications in the pathogenesis of cancer vol.242, pp.2, 2017, https://doi.org/10.1177/1535370216669834
  7. Prognostic value of Rho GDP dissociation inhibitors in patients with hepatocellular carcinoma following liver transplantation vol.14, pp.2, 2017, https://doi.org/10.3892/ol.2017.6333
  8. The prognostic values of the peroxiredoxins family in ovarian cancer vol.38, pp.5, 2018, https://doi.org/10.1042/BSR20180667