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Heat Shock Protein Association with Clinico-Pathological Characteristics of Gastric Cancer in Jordan : HSP70 is Predictive of Poor Prognosis

  • Bodoor, Khaldon (Department of Applied Biology. Jordan University of Science and Technology) ;
  • Jalboush, Sara Abu (Department of Applied Biology. Jordan University of Science and Technology) ;
  • Matalka, Ismail (Department of Pathology, Faculty of Medicine, Jordan University of Science and Technology) ;
  • Abu-Sheikha, Aya (Department of Applied Biology. Jordan University of Science and Technology) ;
  • Waqfi, Rofieda Al (Department of Pathology, Faculty of Medicine, Jordan University of Science and Technology) ;
  • Ebwaini, Hanadi (Department of Pathology, Faculty of Medicine, Jordan University of Science and Technology) ;
  • Abu-Awad, Aymen (Yarmouk University, Faculty of Medicine) ;
  • Fayyad, Luma (Department of Histopathology-King Hussein Medical Center) ;
  • Al-Arjat, Jamal (Department of Histopathology-King Hussein Medical Center) ;
  • Haddad, Yazan (Department of Chemistry and Biochemistry, Faculty of Agronomy, Mendel University in Brno)
  • Published : 2016.08.01

Abstract

Gastric cancer (GC) is a major health problem worldwide and is one of the ten most commonly diagnosed cancers in Jordan. GC is usually diagnosed at late aggressive stages in which treatment options are limited. Recently, heat shock proteins (HSPs) were found to be overexpressed in a wide range of malignancies have been considered as promising candidate biomarkers for GC. The aim of this study was to investigate pathogenic roles of a panel of cytosolic HSPs including HSP90, HSP70, HSP60 and HSP27 in GC. Immunohistochemistry was used to assess the level of expression of these proteins in archived tumor samples (N=87) representing various pathological characteristics of GC. HSP90, HSP60 and HSP27 were expressed abundantly in gastric tumors. On the other hand, HSP70 was reduced significantly and also found to be associated with Helicobacter pylori infection in tissues collected from GC patients. Furthermore, HSP27 was found to be associated with the level of differentiation. Our findings indicate a role of HSP70 as a potential prognostic biomarker, patients harboring positive HSP70 expression displaying worse disease free survival than those with negative HSP70 expression. Differential expression of HSPs may play crucial roles in the initiation and progression of GC, and could be exploited as future therapeutic targets.

Keywords

Gastric cancer;heat shock proteins;immunohistochemistry;prognosis

Acknowledgement

Supported by : Jordan University of Science and Technology

References

  1. Abbasi S.Y, El Taani H, Saad A, et al (2011). Advanced gastric cancer in jordan from 2004 to 2008: a study of epidemiology and outcomes. Gastrointest Cancer Res, 4, 122-27.
  2. Arrigo A.P (2005). In search of the molecular mechanism by which small stress proteins counteract apoptosis during cellular differentiation. J Cellular Biochemistry, 94, 241-6. https://doi.org/10.1002/jcb.20349
  3. Axsen W.S, Styer C.M, Solnick J.V (2009). Inhibition of heat shock protein expression by Helicobacter pylori. Microbial Pathogenesis, 47, 231-6. https://doi.org/10.1016/j.micpath.2009.08.002
  4. Berezowska S, Novotny A, Bauer K, et al (2013). Association between HSP90 and Her2 in gastric and gastroesophageal carcinomas. PLoS One, 8, 69098. https://doi.org/10.1371/journal.pone.0069098
  5. Bodoor K, Ghabkari A, Jaradat Z et al (2010). FGFR3 mutational status and protein expression in patients with bladder cancer in a Jordanian population. Cancer Epidemiol, 34, 724-32. https://doi.org/10.1016/j.canep.2010.05.003
  6. Bodoor K, Matalka I, Hayajneh R et al (2012). Evaluation of BCL-6, CD10, CD138 and MUM-1 expression in diffuse large B-cell lymphoma patients: CD138 is a marker of poor prognosis. Asian Pac J Cancer Prev, 13, 3037-46 https://doi.org/10.7314/APJCP.2012.13.7.3037
  7. Bonorino C and Souza A.P (2007). Hsp70 in tumors: Friend or foe? In 'Heat Shock Proteins in Cancer'. Springer, Netherlands, 191-208.
  8. Bray F, Jemal A, Grey N, et al (2012). Global cancer transitions according to the Human Development Index (2008-2030): a population-based study. Lancet Oncol, 13, 790-801. https://doi.org/10.1016/S1470-2045(12)70211-5
  9. Canoz O, Belenli O, Patiroglu T.E (2002). General features of gastric carcinomas and comparison of HSP70 and NK cell immunoreactivity with prognostic factors. Pathol Oncol Res, 8, 262-9. https://doi.org/10.1007/BF03036742
  10. Cappello F, David S, Ardizzone N, et al (2006). Expression of heat shock proteins HSP10, HSP27, HSP60, HSP70, and HSP90 in urothelial carcinoma of urinary bladder. J Cancer Mol, 2, 73-7.
  11. Ciocca D.R and Calderwood S.K (2005). Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones, 10, 86-103. https://doi.org/10.1379/CSC-99r.1
  12. Correa P (1992). Human gastric carcinogenesis: a multistep and multifactorial process-first American cancer society award lecture on cancer epidemiology and prevention. Cancer Res, 52, 6735-40.
  13. Dudeja V, Vickers S.M, Saluja A.K (2009). The role of heat shock proteins in gastrointestinal diseases. Gut, 58, 1000-9. https://doi.org/10.1136/gut.2007.140194
  14. Ferro A, Peleteiro B, Malvezzi M, et al (2014). Worldwide trends in gastric cancer mortality (1980-2011), with predictions to 2015, and incidence by subtype. Eur J Cancer, 50, 1330-44. https://doi.org/10.1016/j.ejca.2014.01.029
  15. Galluzzi L, Giordanetto F, Kroemer G (2009). Targeting HSP70 for cancer therapy. Molecular Cell, 36, 176-77. https://doi.org/10.1016/j.molcel.2009.10.003
  16. Giaginis C, Daskalopoulou S.S, Vgenopoulou S, et al (2009). Heat Shock Protein-27,-60 and-90 expression in gastric cancer: association with clinicopathological variables and patient survival. BMC Gastroenterol, 9, 14. https://doi.org/10.1186/1471-230X-9-14
  17. Howe MK, Bodoor K, Carlson DA, et al (2014). Identification of an allosteric small-molecule inhibitor selective for the inducible form of heat shock protein 70. Chem Biol, 21, 1648-59. https://doi.org/10.1016/j.chembiol.2014.10.016
  18. Hu B, El Hajj N, Sittler S, et al (2012). Gastric cancer: Classification, histology and application of molecular pathology. J Gastrointestinal Oncol, 3, 251-61.
  19. IARC (International Agency for Research on Cancer) (2012) GLOBOCAN 2012. Lyon, France, IARC. URL: http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx.
  20. Isomoto H, Oka M, Yano Y, et al (2003). Expression of heat shock protein (Hsp) 70 and Hsp 40 in gastric cancer. Cancer Letters, 198, 219-28. https://doi.org/10.1016/S0304-3835(03)00305-7
  21. JCR (Jordan Cancer Registry) (2010). Cancer Incidence in Jordan-2010. Amman, Jordan: Ministry of Health. URL: http://apps.moh.gov.jo/MOH/En/publications.php.
  22. Jiancheng G, Xueyong Z, Yunsheng Y (1999). Overexpression of heat shock protein (HSP) 70 in human gastric cancer. Chinese J Cancer, 1, 13.
  23. Kang Y, Jung W.Y, Lee H, et al (2013). Prognostic significance of heat shock protein 70 expression in early gastric carcinoma. Korean J Pathol, 47, 219-6. https://doi.org/10.4132/KoreanJPathol.2013.47.3.219
  24. Kapranos N, Kominea A, Konstantinopoulos P, et al (2002). Expression of the 27-kDa heat shock protein (HSP27) in gastric carcinomas and adjacent normal, metaplastic, and dysplastic gastric mucosa, and its prognostic significance. J Cancer Res Clin Oncol, 128, 426-2. https://doi.org/10.1007/s00432-002-0357-y
  25. Kaul Z, Yaguchi T, Kaul S.C, et al (2006). Quantum dotbased protein imaging and functional significance of two mitochondrial chaperones in cellular senescence and carcinogenesis, Ann N Y Acad Sci, 1, 469-73.
  26. Kawanishi K, Shiozaki H, Doki Y, et al (1999). Prognostic significance of heat shock proteins 27 and 70 in patients with squamous cell carcinoma of the esophagus. Cancer, 85, 1649-7. https://doi.org/10.1002/(SICI)1097-0142(19990415)85:8<1649::AID-CNCR2>3.0.CO;2-V
  27. Kocevar N, Odreman F, Vindigni A, et al (2012). Proteomic analysis of gastric cancer and immunoblot validation of potential biomarkers. World J Gastroenterol, 18, 1216-28. https://doi.org/10.3748/wjg.v18.i11.1216
  28. Koga F, Kihara K, Neckers L (2009). Inhibition of cancer invasion and metastasis by targeting the molecular chaperone heat-shock protein 90. Anticancer Res, 29, 797-7.
  29. Kumar V, Abbas A.K, Fausto N, et al (2010). Robbins and Cotran Pathologic Basis of Disease, Eighth ed., Philadelphia, Saunders Elsevier.
  30. Lang S.A, Klein D, Moser C, et al (2007). Inhibition of heat shock protein 90 impairs epidermal growth factor–mediated signaling in gastric cancer cells and reduces tumor growth and vascularization in vivo. Molecular Cancer Therapeutics, 6, 1123-2. https://doi.org/10.1158/1535-7163.MCT-06-0628
  31. Lanneau D, De Thonel A, Maurel S, et al (2007). Apoptosis versus cell differentiation: role of heat shock proteins HSP90, HSP70 and HSP27. Prion, 1, 53-60. https://doi.org/10.4161/pri.1.1.4059
  32. Lastraioli E, Raffaella Romoli M, Arcangeli A (2012). Immunohistochemical biomarkers in gastric cancer research and management. Int J Surgical Oncol, 2012,
  33. Lauren P (1965). The two histological main types of gastric carcinoma. Diffuse and so-called intestinal type carcinoma. Acta Pathologica et Microbiologica Scandinavica 64, 31-9. https://doi.org/10.1111/apm.1965.64.1.31
  34. Layke J.C, Lopez P.P (2004). Gastric cancer: diagnosis and treatment options. American Family Physician, 69, 1133-41.
  35. Lee H.W, Lee E.H, Kim S.H, et al (2013). Heat shock protein 70 (HSP70) expression is associated with poor prognosis in intestinal type gastric cancer. Virchows Archiv, 463, 489-5. https://doi.org/10.1007/s00428-013-1461-x
  36. Lianos G.D, Alexiou G.A, Mangano A, et al (2015). The role of heat shock proteins in cancer. Cancer Letters, 360, 114-8. https://doi.org/10.1016/j.canlet.2015.02.026
  37. Liu W, Chen Y, Lu G, Sun L, Si J (2011). Down-regulation of HSP70 sensitizes gastric epithelial cells to apoptosis and growth retardation triggered by H. Pylori. BMC Gastroenterol, 11, 146. https://doi.org/10.1186/1471-230X-11-146
  38. Maehara Y, Oki E, Abe T, et al (2000). Overexpression of the heat shock protein HSP70 family and p53 protein and prognosis for patients with gastric cancer. Oncol, 58, 144-1. https://doi.org/10.1159/000012091
  39. Murphy M.E (2013). The HSP70 family and cancer. Carcinogenesis, 34, 1181-8. https://doi.org/10.1093/carcin/bgt111
  40. Nagata Y, Kudo M, Nagai T, et al (2012). Heat shock protein 27 expression is inversely correlated with atrophic gastritis and intraepithelial neoplasia. Digestive Diseases and Sciences, 58, 381-8.
  41. Nagini S (2012). Carcinoma of the stomach: A review of epidemiology, pathogenesis, molecular genetics and chemoprevention. World J Gastrointestinal Oncol, 4, 156. https://doi.org/10.4251/wjgo.v4.i7.156
  42. Pierzchalski P, Krawiec A, Ptak-Belowska A, et al (2006). The mechanism of heat-shock protein 70 gene expression abolition in gastric epithelium caused by Helicobacter pylori infection. Helicobacter, 11, 96-4. https://doi.org/10.1111/j.1523-5378.2006.00383.x
  43. Schmitt E, Gehrmann M, Brunet M, Multhoff G, Garrido C (2007). Intracellular and extracellular functions of heat shock proteins: repercussions in cancer therapy. J Leukocyte Biol, 81, 15-7. https://doi.org/10.1189/jlb.0306167
  44. Seigneuric R, Mjahed H, Gobbo J (2011). Heat shock proteins as danger signals for cancer detection. Frontiers Oncol, 1, 37.
  45. Sherman M, Multhoff G (2007). Heat shock proteins in cancer. Ann New York Acad Sci, 1113, 192-1. https://doi.org/10.1196/annals.1391.030
  46. Shibata W, Hirata Y, Yoshida H, et al (2005). NF-kappaB and ERK-signaling pathways contribute to the gene expression induced by cag PAI-positive-Helicobacter pylori infection. World J Gastroenterol, 11, 6134-43. https://doi.org/10.3748/wjg.v11.i39.6134
  47. Solit D.B, Rosen N (2006). Hsp90: a novel target for cancer therapy. Curr Topics Medicinal Chemistry, 6, 1205-14. https://doi.org/10.2174/156802606777812068
  48. Targosz A, Brzozowski T, Pierzchalski P, et al (2012). Helicobacter pylori promotes apoptosis, activates cyclooxygenase (COX)- 2 and inhibits heat shock protein HSP70 in gastric cancer epithelial cells. Inflamm Res, 61, 955-66. https://doi.org/10.1007/s00011-012-0487-x
  49. Tokunaga Y, Shirahase H, Hoppou T, et al (2000). Density of Helicobacter pylori infection evaluated semiquantitatively in gastric cancer. J Clin Gastroenterol, 31, 217-21. https://doi.org/10.1097/00004836-200010000-00006
  50. Tsan M.F, Gao B (2004). Cytokine function of heat shock proteins. American J Physiology-Cell Physiol, 286, 739-44.
  51. Wang T, Echeverria P.C, Picard D (2013). Overview of molecular chaperones in health and disease, inhibitors of molecular chaperones as therapeutic agents. 1, 1-36
  52. Wang X.P, Wang Q.X, Ying X.P (2007). Correlation between clinicopathology and expression of heat shock protein 72 and glycoprotein 96 in human gastric adenocarcinoma. Tohoku J Experimental Med, 212, 35-41. https://doi.org/10.1620/tjem.212.35
  53. Wei L, Liu T.T, Wang H.H, et al (2011). Hsp27 participates in the maintenance of breast cancer stem cells through regulation of epithelial-mesenchymal transition and nuclear factorkappaB. Breast Cancer Res, 13, 101. https://doi.org/10.1186/bcr2793
  54. Wettstein G, Bellaye PS, Kolb M, et al (2013). Inhibition of HSP27 blocks fibrosis development and EMT features by promoting Snail degradation. FASEB J, 27, 1549-60. https://doi.org/10.1096/fj.12-220053
  55. Whitesell L, Lindquist S.L (2005). HSP90 and the chaperoning of cancer. Nat Rev Cancer, 5, 761-72. https://doi.org/10.1038/nrc1716
  56. Wroblewski LE, Peek RM, Wilson KT (2010). Helicobacter pylori and gastric cancer: factors that modulate disease risk. Clin Microbiol Rev, 23, 713-39. https://doi.org/10.1128/CMR.00011-10
  57. Xiang T.X, Li Y, Jiang Z, et al (2008). RNA interferencemediated silencing of the Hsp70 gene inhibits human gastric cancer cell growth and induces apoptosis in vitro and in vivo. Tumori, 94, 539-50. https://doi.org/10.1177/030089160809400416
  58. Xu X, Wang W, Shao W, et al (2011). Heat shock protein-60 expression was significantly correlated with the prognosis of lung adenocarcinoma. J Surgical Oncol, 104, 598-603. https://doi.org/10.1002/jso.21992
  59. Zhao Z.G and Shen W.L (2005). Heat shock protein 70 antisense oligonucleotide inhibits cell growth and induces apoptosis in human gastric cancer cell line SGC-7901. World J Gastroenterol, 11, 73-8. https://doi.org/10.3748/wjg.v11.i1.73
  60. Zoubeidi A and Gleave M (2012). Small heat shock proteins in cancer therapy and prognosis. Int J Biochem Cell Biol, 44, 1646-56. https://doi.org/10.1016/j.biocel.2012.04.010
  61. Zuo D.S, Dai J, Bo A.H, Fan J, et al (2003). Significance of expression of heat shock protein90 in human gastric cancer. World J Gastroenterol, 9, 2616-8. https://doi.org/10.3748/wjg.v9.i11.2616
  62. Lebret T, Watson R.W.G, Molinie V, et al (2003). Heat shock proteins HSP27, HSP60, HSP70, and HSP90. Cancer, 98, 970-7. https://doi.org/10.1002/cncr.11594