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Prognostic value of HIF-1α expression in patients with gastric cancer

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Abstract

The role of hypoxia-inducible factors-1 alpha (HIF-1α) expression in gastric cancer remains controversial. We performed a systematic review of the literature with meta-analysis. Electronic databases were used to identify published studies before December 1, 2012. Pooled hazard ratio (HR) or odds ratio (OR) with 95 % confidence interval (95 % CI) was used to estimate the strength of the association between HIF-1α expression and survival of gastric cancer patients. Heterogeneity and publication bias were also assessed. Final analysis of 1,268 patients from 9 eligible studies was performed. High HIF-1α expression was significantly correlated with poor overall survival (OS) of gastric cancer patients (HR = 2.14, 95 % CI = 1.32–3.48). Subgroup analysis indicated that HIF-1α over-expression had an unfavorable impact on OS in Asian patients (HR = 2.35, 95 % CI = 1.41–3.92). Moreover, up-regulation of HIF-1α was significantly associated with the depth of invasion (OR = 2.49, 95 % CI = 1.28–4.83), lymph node metastasis (OR = 2.15, 95 % CI = 1.27–3.66), and vascular invasion (OR = 2.23, 95 % CI = 1.20–4.14). HIF-1α expression might be a predicative factor of poor prognosis for gastric cancer particularly in Asia.

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References

  1. Ferlay J, Shin HR, Bray F et al (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127(12):2893–2917

    Article  PubMed  CAS  Google Scholar 

  2. Amedei A, Benagiano M, della Bella C et al (2011) Novel immunotherapeutic strategies of gastric cancer treatment. J Biomed Biotechnol 2011:437348

    Article  PubMed  Google Scholar 

  3. Keighley MR (2003) Gastrointestinal cancers in Europe. Aliment Pharmacol Ther 18(Suppl 3):7–30

    Article  PubMed  Google Scholar 

  4. Xing X, Tang YB, Yuan G et al (2012) The prognostic value of E-cadherin in gastric cancer: A meta-analysis. Int J Cancer

  5. Zhang QW, Liu L, Chen R et al (2012) Matrix metalloproteinase-9 as a prognostic factor in gastric cancer: a meta-analysis. Asian Pac J Cancer Prev 13(6):2903–2908

    Article  PubMed  Google Scholar 

  6. Liu L, Ma XL, Xiao ZL et al (2012) Prognostic value of vascular endothelial growth factor expression in resected gastric cancer. Asian Pac J Cancer Prev 13(7):3089–3097

    Article  PubMed  Google Scholar 

  7. O’Rourke JF, Dachs GU, Gleadle JM et al (1997) Hypoxia response elements. Oncol Res 9(6–7):327–332

    PubMed  Google Scholar 

  8. Rohwer N, Cramer T (2010) HIFs as central regulators of gastric cancer pathogenesis. Cancer Biol Ther 10(4):383–385

    Article  PubMed  CAS  Google Scholar 

  9. Zagzag D, Zhong H, Scalzitti JM et al (2000) Expression of hypoxia-inducible factor 1 alpha in brain tumors: association with angiogenesis, invasion, and progression. Cancer 88(11):2606–2618

    Article  PubMed  CAS  Google Scholar 

  10. Theodoropoulos VE, Lazaris ACh, Sofras F et al (2004) Hypoxia-inducible factor 1 alpha expression correlates with angiogenesis and unfavorable prognosis in bladder cancer. Eur Urol 46(2):200–208

    Article  PubMed  CAS  Google Scholar 

  11. Bos R, Zhong H, Hanrahan CF et al (2001) Levels of hypoxia-inducible factor 1 alpha during breast carcinogenesis. J Natl Cancer Inst 93(4):309–314

    Article  PubMed  CAS  Google Scholar 

  12. Kuwai T, Kitadai Y, Tanaka S et al (2003) Expression of hypoxia-inducible factor 1 alpha is associated with tumor vascularization in human colorectal carcinoma. Int J Cancer 105(2):176–181

    Article  PubMed  CAS  Google Scholar 

  13. Bos R, van der Groep P, Greijer AE et al (2003) Levels of hypoxia-inducible factor-1alpha independently predict prognosis in patients with lymph node negative breast carcinoma. Cancer 97(6):1573–1581

    Article  PubMed  Google Scholar 

  14. Kurokawa T, Miyamoto M, Kato K et al (2003) Overexpression of hypoxia-inducible-factor 1 alpha (HIF-1alpha) in oesophageal squamous cell carcinoma correlates with lymph node metastasis and pathologic stage. Br J Cancer 89(6):1042–1047

    Article  PubMed  CAS  Google Scholar 

  15. Parmar MK, Torri V, Stewart L (1998) Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med 17(24):2815–2834

    Article  PubMed  CAS  Google Scholar 

  16. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558

    Article  PubMed  Google Scholar 

  17. Egger M, Davey Smith G, Schneider M et al (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634

    Article  PubMed  CAS  Google Scholar 

  18. Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50(4):1088–1101

    Article  PubMed  CAS  Google Scholar 

  19. Mizokami K, Kakeji Y, Oda S et al (2006) Relationship of hypoxia-inducible factor 1alpha and p21WAF1/CIP1 expression to cell apoptosis and clinical outcome in patients with gastric cancer. World J Surg Oncol 4:94

    Article  PubMed  Google Scholar 

  20. Cabuk D, Basaran G, Celikel C et al (2007) Vascular endothelial growth factor, hypoxia-inducible factor 1 alpha and CD34 expressions in early-stage gastric tumors: relationship with pathological factors and prognostic impact on survival. Oncology 72(1–2):111–117

    Article  PubMed  CAS  Google Scholar 

  21. Nakamura J, Kitajima Y, Kai K et al (2009) Hypoxia-inducible factor-1alpha expression predicts the response to 5-fluorouracil-based adjuvant chemotherapy in advanced gastric cancer. Oncol Rep 22(4):693–699

    PubMed  CAS  Google Scholar 

  22. Nakamura J, Kitajima Y, Kai K et al (2010) HIF-1alpha is an unfavorable determinant of relapse in gastric cancer patients who underwent curative surgery followed by adjuvant 5-FU chemotherapy. Int J Cancer 127(5):1158–1171

    Article  PubMed  CAS  Google Scholar 

  23. Woo S, Lee BL, Yoon J et al (2011) Constitutive activation of signal transducers and activators of transcription 3 correlates with better prognosis, cell proliferation and hypoxia-inducible factor-1α in human gastric cancer. Pathobiology 78(6):295–301

    Article  PubMed  CAS  Google Scholar 

  24. Mizokami K, Kakeji Y, Oda S et al (2006) Clinicopathologic significance of hypoxia-inducible factor 1alpha overexpression in gastric carcinomas. J Surg Oncol 94(2):149–154

    Article  PubMed  CAS  Google Scholar 

  25. Sumiyoshi Y, Kakeji Y, Egashira A et al (2006) Overexpression of hypoxia-inducible factor 1alpha and p53 is a marker for an unfavorable prognosis in gastric cancer. Clin Cancer Res 12(17):5112–5117

    Article  PubMed  CAS  Google Scholar 

  26. Urano N, Fujiwara Y, Doki Y et al (2006) Overexpression of hypoxia-inducible factor-1 alpha in gastric adenocarcinoma. Gastric Cancer 9(1):44–49

    Article  PubMed  CAS  Google Scholar 

  27. Ma J, Zhang L, Ru GQ et al (2007) Upregulation of hypoxia inducible factor 1alpha mRNA is associated with elevated vascular endothelial growth factor expression and excessive angiogenesis and predicts a poor prognosis in gastric carcinoma. World J Gastroenterol 13(11):1680–1686

    PubMed  CAS  Google Scholar 

  28. Griffiths EA, Pritchard SA, Valentine HR et al (2007) Hypoxia-inducible factor-1alpha expression in the gastric carcinogenesis sequence and its prognostic role in gastric and gastro-oesophageal adenocarcinomas. Br J Cancer 96(1):95–103

    Article  PubMed  CAS  Google Scholar 

  29. Oh SY, Kwon HC, Kim SH et al (2008) Clinicopathologic significance of HIF-1alpha, p53, and VEGF expression and preoperative serum VEGF level in gastric cancer. BMC Cancer 8:123

    Article  PubMed  Google Scholar 

  30. Kolev Y, Uetake H, Takagi Y et al (2008) Lactate dehydrogenase-5 (LDH-5) expression in human gastric cancer: association with hypoxia-inducible factor (HIF-1alpha) pathway, angiogenic factors production and poor prognosis. Ann Surg Oncol 15(8):2336–2344

    Article  PubMed  Google Scholar 

  31. Qiu MZ, Han B, Luo HY et al (2011) Expressions of hypoxia-inducible factor-1α and hexokinase-II in gastric adenocarcinoma: the impact on prognosis and correlation to clinicopathologic features. Tumour Biol 32(1):159–166

    Article  PubMed  CAS  Google Scholar 

  32. Isobe T, Aoyagi K, Koufuji K et al (2012) Clinicopathological significance of hypoxia-inducible factor-1 alpha (HIF-1α) expression in gastric cancer. Int J Clin Oncol

  33. Stoeltzing O, McCarty MF, Wey JS et al (2004) Role of hypoxia-inducible factor 1 alpha in gastric cancer cell growth, angiogenesis, and vessel maturation. J Natl Cancer Inst 96(12):946–956

    Article  PubMed  CAS  Google Scholar 

  34. Malats N, Bustos A, Nascimento CM et al (2005) P53 as a prognostic marker for bladder cancer: a meta-analysis and review. Lancet Oncol 6(9):678–686

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was partly supported by the Grants from Committee of Education project of Anhui province (Code: KJ2012A151), and the National Natural Science Foundation of China (81272397). We thank all the people who give the help for this study.

Conflict of interest

The auhtors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of General Surgery, Anhui Provincial Hospital Affiliated with Anhui Medical University, and Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, 17 Lujiang Road, Hefei, 230001, Anhui, China

    Cheng-lin Zhu, Qiang Huang, Chen-hai Liu, Xian-sheng Lin & Fang Xie

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  1. Cheng-lin Zhu
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  2. Qiang Huang
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  3. Chen-hai Liu
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  4. Xian-sheng Lin
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  5. Fang Xie
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Correspondence to Qiang Huang.

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Zhu, Cl., Huang, Q., Liu, Ch. et al. Prognostic value of HIF-1α expression in patients with gastric cancer. Mol Biol Rep 40, 6055–6062 (2013). https://doi.org/10.1007/s11033-013-2715-z

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  • DOI: https://doi.org/10.1007/s11033-013-2715-z

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