Advertisement

Tumor Biology

, Volume 35, Issue 11, pp 10871–10877 | Cite as

Identification of glutathione S-transferase omega 1 (GSTO1) protein as a novel tumor-associated antigen and its autoantibody in human esophageal squamous cell carcinoma

  • Yang Li
  • Qi Zhang
  • Bo Peng
  • Qing Shao
  • Wei Qian
  • Jian-Ying Zhang
Research Article

Abstract

Esophageal squamous cell carcinoma (ESCC) is the main form of esophageal malignancy. The approach for early diagnosis of this malignancy is very limited. In the present study, we first evaluated glutathione S-transferase omega 1 (GSTO1), a protein related to metabolism, as a tumor-associated antigen in ESCC, and we also evaluated its autoantibody as a potential biomarker in early detection of ESCC. First, immunohistochemistry (IHC) analysis of GSTO1 protein expression in esophageal tissues showed that the percentage of positive staining of GSTO1 in ESCC tissues was 87.5 % while there was no positive staining in adjacent tissues or normal tissues, indicating that overexpression of GSTO1 is closely related to ESCC. Then, enzyme-linked immunosorbent assay (ELISA) showed that the frequency of detectable autoantibody against GSTO1 in patients’ sera totals 44.8 %. In contrast, the frequency of detectable autoantibody was only 6.7 % in normal human sera (p < 0.01). To further evaluate our ELISA results, western blotting and immunofluorescence assay were also performed. The results were consistent with the data from ELISA. In conclusion, the current study has demonstrated that GSTO1 protein is overexpressed in ESCC and can induce a detectable autoantibody response, which may serve as a potential biomarker in the early detection of ESCC.

Keywords

Esophageal squamous cell carcinoma (ESCC) Glutathione S-transferase omega 1(GSTO1) Tumor-associated antigen (TAA) Autoantibody 

Notes

Acknowledgments

The authors thank Dr. Eng M. Tan (The Scripps Research Institute) for his support. This work was supported by a grant (SCICA 166016) from the National Institutes of Health (NIH). They also thank the Border Biological Research Center (BBRC) Core Facilities at The University of Texas at El Paso (UTEP) for their support, which were funded by NIH grant (5G12MD007590).

Conflicts of interest

None

References

  1. 1.
    Lagergren J, Ye W, Lagergren P, Lu Y. The risk of esophageal adenocarcinoma after antireflux surgery. Gastroenterology. 2010;138:1297–301.PubMedCrossRefGoogle Scholar
  2. 2.
    Lindkvist B, Johansen D, Stocks T, Concin H, Bjorge T, Almquist M, et al. Metabolic risk factors for esophageal squamous cell carcinoma and adenocarcinoma: a prospective study of 580,000 subjects within the me-can project. BMC Cancer. 2014;14:103.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Hongo M, Nagasaki Y, Shoji T. Epidemiology of esophageal cancer: orient to occident. Effects of chronology, geography and ethnicity. J Gastroenterol Hepatol. 2009;24:729–35.PubMedCrossRefGoogle Scholar
  4. 4.
    Tran GD, Sun XD, Abnet CC, Fan JH, Dawsey SM, Dong ZW, et al. Prospective study of risk factors for esophageal and gastric cancers in the Linxian general population trial cohort in China. Int J Cancer. 2005;113:456–63.PubMedCrossRefGoogle Scholar
  5. 5.
    Stolzenberg-Solomon RZ, Qiao YL, Abnet CC, Ratnasinghe DL, Dawsey SM, Dong ZW, et al. Esophageal and gastric cardia cancer risk and folate- and vitamin B(12)-related polymorphisms in Linxian, China. Cancer Epidemiol Biomarkers Prev. 2003;12:1222–6.PubMedGoogle Scholar
  6. 6.
    von Brevern MC, Hollstein MC, Cawley HM, De Benedetti VM, Bennett WP, Liang L, et al. Circulating anti-p53 antibodies in esophageal cancer patients are found predominantly in individuals with p53 core domain mutations in their tumors. Cancer Res. 1996;56:4917–21.Google Scholar
  7. 7.
    Soussi T. p53 antibodies in the sera of patients with various types of cancer: a review. Cancer Res. 2000;60:1777–88.PubMedGoogle Scholar
  8. 8.
    Yu M, Zhan Q, Finn OJ. Immune recognition of cyclin B1 as a tumor antigen is a result of its overexpression in human tumors that is caused by non-functional p53. Mol Immunol. 2002;38:981–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Zhang JY, Tan EM. Autoantibodies to tumor-associated antigens as diagnostic biomarkers in hepatocellular carcinoma and other solid tumors. Expert Rev Mol Diagn. 2010;10:321–8.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Tan HT, Low J, Lim SG, Chung MC. Serum autoantibodies as biomarkers for early cancer detection. FEBS J. 2009;276:6880–904.PubMedCrossRefGoogle Scholar
  11. 11.
    Zhang J, Wang K, Zhang J, Liu SS, Dai L, Zhang JY. Using proteomic approach to identify tumor-associated proteins as biomarkers in human esophageal squamous cell carcinoma. J Proteome Res. 2011;10:2863–72.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Board PG, Coggan M, Chelvanayagam G, Easteal S, Jermiin LS, Schulte GK, et al. Identification, characterization, and crystal structure of the omega class glutathione transferases. J Biol Chem. 2000;275:24798–806.PubMedCrossRefGoogle Scholar
  13. 13.
    Maellaro E, Del Bello B, Sugherini L, Comporti M, Casini AF. Purification and characterization of glutathione-dependent dehydroascorbate reductase from rat liver. Methods Enzymol. 1997;279:30–5.PubMedCrossRefGoogle Scholar
  14. 14.
    Whitbread AK, Masoumi A, Tetlow N, Schmuck E, Coggan M, Board PG. Characterization of the omega class of glutathione transferases. Methods Enzymol. 2005;401:78–99.PubMedCrossRefGoogle Scholar
  15. 15.
    Kodym R, Calkins P, Story M. The cloning and characterization of a new stress response protein. A mammalian member of a family of theta class glutathione S-transferase-like proteins. J Biol Chem. 1999;274:5131–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Li YJ, Oliveira SA, Xu P, Martin ER, Stenger JE, Scherzer CR, et al. Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease. Hum Mol Genet. 2003;12:3259–67.PubMedCrossRefGoogle Scholar
  17. 17.
    Li YJ, Scott WK, Zhang L, Lin PI, Oliveira SA, Skelly T, et al. Revealing the role of glutathione S-transferase omega in age-at-onset of Alzheimer and Parkinson diseases. Neurobiol Aging. 2006;27:1087–93.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Kolsch H, Larionov S, Dedeck O, Orantes M, Birkenmeier G, Griffin WS, et al. Association of the glutathione S-transferase omega-1 Ala140Asp polymorphism with cerebrovascular atherosclerosis and plaque-associated interleukin-1 alpha expression. Stroke. 2007;38:2847–50.PubMedCrossRefGoogle Scholar
  19. 19.
    Kolsch H, Linnebank M, Lutjohann D, Jessen F, Wullner U, Harbrecht U, et al. Polymorphisms in glutathione S-transferase omega-1 and AD, vascular dementia, and stroke. Neurology. 2004;63:2255–60.PubMedCrossRefGoogle Scholar
  20. 20.
    Harju TH, Peltoniemi MJ, Rytila PH, Soini Y, Salmenkivi KM, Board PG, et al. Glutathione S-transferase omega in the lung and sputum supernatants of copd patients. Respir Res. 2007;8:48.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Yanbaeva DG, Wouters EF, Dentener MA, Spruit MA, Reynaert NL. Association of glutathione-S-transferase omega haplotypes with susceptibility to chronic obstructive pulmonary disease. Free Radic Res. 2009;43:738–43.PubMedCrossRefGoogle Scholar
  22. 22.
    Pongstaporn W, Pakakasama S, Sanguansin S, Hongeng S, Petmitr S. Polymorphism of glutathione S-transferase omega gene: association with risk of childhood acute lymphoblastic leukemia. J Cancer Res Clin Oncol. 2009;135:673–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Masoudi M, Saadat I, Omidvari S, Saadat M. Genetic polymorphisms of GSTO2, GSTM1, and GSTT1 and risk of gastric cancer. Mol Biol Rep. 2009;36:781–4.PubMedCrossRefGoogle Scholar
  24. 24.
    Liu X, Chai Y, Li J, Ren P, Liu M, Dai L, et al. Autoantibody response to a novel tumor-associated antigen p90/CIP2a in breast cancer immunodiagnosis. Tumour Biol. 2014;35:2661–7.PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Chen JH, Ni RZ, Xiao MB, Guo JG, Zhou JW. Comparative proteomic analysis of differentially expressed proteins in human pancreatic cancer tissue. Hepatobiliary Pancreat Dis Int. 2009;8:193–200.PubMedGoogle Scholar
  26. 26.
    Piaggi S, Marchi S, Ciancia E, Debortoli N, Lazzarotti A, Saviozzi M, et al. Nuclear translocation of glutathione transferase omega is a progression marker in Barrett’s esophagus. Oncol Rep. 2009;21:283–7.PubMedGoogle Scholar
  27. 27.
    Yan XD, Pan LY, Yuan Y, Lang JH, Mao N. Identification of platinum-resistance associated proteins through proteomic analysis of human ovarian cancer cells and their platinum-resistant sublines. J Proteome Res. 2007;6:772–80.PubMedCrossRefGoogle Scholar
  28. 28.
    Yin ZL, Dahlstrom JE, Le Couteur DG, Board PG. Immunohistochemistry of omega class glutathione S-transferase in human tissues. J Histochem Cytochem. 2001;49:983–7.PubMedCrossRefGoogle Scholar
  29. 29.
    Burmeister C, Luersen K, Heinick A, Hussein A, Domagalski M, Walter RD, et al. Oxidative stress in Caenorhabditis elegans: protective effects of the omega class glutathione transferase (GSTO-1). FASEB J. 2008;22:343–54.PubMedCrossRefGoogle Scholar
  30. 30.
    Berry MF. Esophageal cancer: staging system and guidelines for staging and treatment. J Thorac Dis. 2014;6:S289–97.PubMedCentralPubMedGoogle Scholar
  31. 31.
    Jessri M, Rashidkhani B, Hajizadeh B, Jessri M, Gotay C. Macronutrients, vitamins and minerals intake and risk of esophageal squamous cell carcinoma: a case–control study in Iran. Nutr J. 2011;10:137.PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Song PI, Liang H, Fan JH, Wei WQ, Wang GQ, Qiao YL. Long-term survival after esophagectomy for early esophageal squamous cell carcinoma in Linxian, China. J Surg Oncol. 2011;104:176–80.PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Piaggi S, Raggi C, Corti A, Pitzalis E, Mascherpa MC, Saviozzi M, et al. Glutathione transferase omega 1–1 (GSTO1-1) plays an anti-apoptotic role in cell resistance to cisplatin toxicity. Carcinogenesis. 2010;31:804–11.PubMedCrossRefGoogle Scholar
  34. 34.
    Dulhunty A, Gage P, Curtis S, Chelvanayagam G, Board P. The glutathione transferase structural family includes a nuclear chloride channel and a ryanodine receptor calcium release channel modulator. J Biol Chem. 2001;276:3319–23.PubMedCrossRefGoogle Scholar
  35. 35.
    Bei R, Masuelli L, Palumbo C, Modesti M, Modesti A. A common repertoire of autoantibodies is shared by cancer and autoimmune disease patients: inflammation in their induction and impact on tumor growth. Cancer Lett. 2009;281:8–23.PubMedCrossRefGoogle Scholar
  36. 36.
    Pihoker C, Gilliam LK, Hampe CS, Lernmark A. Autoantibodies in diabetes. Diabetes. 2005;54 Suppl 2:S52–61.PubMedCrossRefGoogle Scholar
  37. 37.
    Xu YW, Peng YH, Chen B, Wu ZY, Wu JY, Shen JH, et al. Autoantibodies as potential biomarkers for the early detection of esophageal squamous cell carcinoma. Am J Gastroenterol. 2014;109:36–45.PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Zaenker P, Ziman MR. Serologic autoantibodies as diagnostic cancer biomarkers—a review. Cancer Epidemiol Biomarkers Prev. 2013;22:2161–81.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Yang Li
    • 1
  • Qi Zhang
    • 1
  • Bo Peng
    • 1
  • Qing Shao
    • 1
  • Wei Qian
    • 1
    • 2
  • Jian-Ying Zhang
    • 1
  1. 1.Department of Biological SciencesThe University of Texas at El PasoEl PasoUSA
  2. 2.Sino-Dutch Biomedical and Information Engineering SchoolNortheastern UniversityShenyangChina

Personalised recommendations