Skip to main content

Advertisement

Log in

Role of survivin as prognostic and clinicopathological marker in gastric cancer: a meta-analysis

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Survivin has been implicated as a potential prognostic marker in a wide range of malignant tumours. However, the prognostic impact of survivin in gastric cancer remains to be controversial and published data are sometimes heterogeneous. Thus, aim of this study was to review the literature by performing an electronical database search via PubMed and EMBASE to identify eligible studies that assessed the impact of survivin as prognostic marker and its association with clinicopathological variables. Database search until November 21st 2012 retrieved 20 studies comprising 2,695 gastric cancer patients that assessed expression of survivin by immunohistochemistry or RT-PCR analyses in gastric cancer specimens. Meta-analyses of clinicopathological variables revealed an association between the expression of survivin and the presence of lymph node metastases (pooled OR: 0.58; 95 % CI 0.35–0.96). In addition, a correlation between the expression of survivin and overall survival for patients with gastric cancer (pooled HR 1.93; 95 % CI 1.51–2.48) became evident. More importantly, we were able to exclude a severe heterogeneity (I2 = 31 %) or publication bias for the survival analyses. Furthermore, one-way sensitivity analysis and subgroup analyses regarding the method used to detect survivin, the type of survival analysis, the study quality and whether information was provided regarding neoadjuvant therapy supported our initial results. In conclusion, this meta-analysis indicates the prognostic significance of survivin in patients with gastric cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Organization WH (2012) Cancer (Fact sheet No. 297). WHO website. Accessed 15 Jan 2013

  2. Kamangar F, Dores GM, Anderson WF (2006) Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol 24(14):2137–2150

    Article  PubMed  Google Scholar 

  3. Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR (2008) Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med 358(1):36–46

    Article  PubMed  CAS  Google Scholar 

  4. Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Risse ML, Ajani JA (2006) Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol 24(31):4991–4997

    Article  PubMed  Google Scholar 

  5. Wagner AD, Moehler M (2009) Development of targeted therapies in advanced gastric cancer: promising exploratory steps in a new era. Curr Opin Oncol 21(4):381–385

    Article  PubMed  CAS  Google Scholar 

  6. Nakajima M, Sawada H, Yamada Y, Watanabe A, Tatsumi M, Yamashita J, Matsuda M, Sakaguchi T, Hirao T, Nakano H (1999) The prognostic significance of amplification and overexpression of c-met and c-erb B-2 in human gastric carcinomas. Cancer 85(9):1894–1902

    PubMed  CAS  Google Scholar 

  7. Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Ruschoff J, Kang YK (2010) Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 376(9742):687–697

    Article  PubMed  CAS  Google Scholar 

  8. Begnami MD, Fukuda E, Fregnani JH, Nonogaki S, Montagnini AL, da Costa WL, Soares FA FA Jr (2011) Prognostic implications of altered human epidermal growth factor receptors (HERs) in gastric carcinomas: HER2 and HER3 are predictors of poor outcome. J Clin Oncol 29(22):3030–3036

    Article  PubMed  CAS  Google Scholar 

  9. Maeda K, Chung YS, Ogawa Y, Takatsuka S, Kang SM, Ogawa M, Sawada T, Sowa M (1996) Prognostic value of vascular endothelial growth factor expression in gastric carcinoma. Cancer 77(5):858–863

    Article  PubMed  CAS  Google Scholar 

  10. Smyth EC, Cunningham D (2012) Targeted therapy for gastric cancer. Curr Treat Options Oncol 13(3):377–389

    Article  PubMed  Google Scholar 

  11. de Almagro MC, Vucic D (2012) The inhibitor of apoptosis (IAP) proteins are critical regulators of signaling pathways and targets for anti-cancer therapy. Exp Oncol 34(3):200–211

    PubMed  Google Scholar 

  12. Ambrosini G, Adida C, Altieri DC (1997) A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 3(8):917–921

    Article  PubMed  CAS  Google Scholar 

  13. Skoufias DA, Mollinari C, Lacroix FB, Margolis RL (2000) Human survivin is a kinetochore-associated passenger protein. J Cell Biol 151(7):1575–1582

    Article  PubMed  CAS  Google Scholar 

  14. Dohi T, Okada K, Xia F, Wilford CE, Samuel T, Welsh K, Marusawa H, Zou H, Armstrong R, Matsuzawa S, Salvesen GS, Reed JC, Altieri DC (2004) An IAP-IAP complex inhibits apoptosis. J Biol Chem 279(33):34087–34090

    Article  PubMed  CAS  Google Scholar 

  15. Mehrotra S, Languino LR, Raskett CM, Mercurio AM, Dohi T, Altieri DC (2010) IAP regulation of metastasis. Cancer Cell 17(1):53–64

    Article  PubMed  CAS  Google Scholar 

  16. Lu CD, Altieri DC, Tanigawa N (1998) Expression of a novel antiapoptosis gene, survivin, correlated with tumor cell apoptosis and p53 accumulation in gastric carcinomas. Cancer Res 58(9):1808–1812

    PubMed  CAS  Google Scholar 

  17. Kawasaki H, Altieri DC, Lu CD, Toyoda M, Tenjo T, Tanigawa N (1998) Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer. Cancer Res 58(22):5071–5074

    PubMed  CAS  Google Scholar 

  18. Krieg A, Mahotka C, Krieg T, Grabsch H, Muller W, Takeno S, Suschek CV, Heydthausen M, Gabbert HE, Gerharz CD (2002) Expression of different survivin variants in gastric carcinomas: first clues to a role of survivin-2B in tumour progression. Br J Cancer 86(5):737–743

    Article  PubMed  CAS  Google Scholar 

  19. Mahotka C, Krieg T, Krieg A, Wenzel M, Suschek CV, Heydthausen M, Gabbert HE, Gerharz CD (2002) Distinct in vivo expression patterns of survivin splice variants in renal cell carcinomas. Int J Cancer 100(1):30–36

    Article  PubMed  CAS  Google Scholar 

  20. Steels E, Paesmans M, Berghmans T, Branle F, Lemaitre F, Mascaux C, Meert AP, Vallot F, Lafitte JJ, Sculier JP (2001) Role of p53 as a prognostic factor for survival in lung cancer: a systematic review of the literature with a meta-analysis. Eur Respir J 18(4):705–719

    Article  PubMed  CAS  Google Scholar 

  21. 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 

  22. Lau J, Ioannidis JP, Schmid CH (1997) Quantitative synthesis in systematic reviews. Ann Intern Med 127(9):820–826

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  24. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188

    Article  PubMed  CAS  Google Scholar 

  25. Yu J, Leung WK, Ebert MP, Ng EK, Go MY, Wang HB, Chung SC, Malfertheiner P, Sung JJ (2002) Increased expression of survivin in gastric cancer patients and in first degree relatives. Br J Cancer 87(1):91–97

    Article  PubMed  CAS  Google Scholar 

  26. Tsuburaya A, Noguchi Y, Yoshikawa T, Saito A, Doi C, Okamoto T, Fukuzawa K (2002) An anti-apoptosis gene, survivin and telomerase expression in gastric cancer. Hepatogastroenterology 49(46):1150–1152

    PubMed  CAS  Google Scholar 

  27. Wakana Y, Kasuya K, Katayanagi S, Tsuchida A, Aoki T, Koyanagi Y, Ishii H, Ebihara Y (2002) Effect of survivin on cell proliferation and apoptosis in gastric cancer. Oncol Rep 9(6):1213–1218

    PubMed  CAS  Google Scholar 

  28. Miyachi K, Sasaki K, Onodera S, Taguchi T, Nagamachi M, Kaneko H, Sunagawa M (2003) Correlation between survivin mRNA expression and lymph node metastasis in gastric cancer. Gastric Cancer 6(4):217–224

    Article  PubMed  CAS  Google Scholar 

  29. Zhu XD, Lin GJ, Qian LP, Chen ZQ (2003) Expression of survivin in human gastric carcinoma and gastric carcinoma model of rats. World J Gastroenterol 9(7):1435–1438

    PubMed  CAS  Google Scholar 

  30. Meng H, Lu C, Mabuchi H, Tanigawa N (2004) Prognostic significance and different properties of survivin splicing variants in gastric cancer. Cancer Lett 216(2):147–155

    Article  PubMed  CAS  Google Scholar 

  31. Nakamura M, Tsuji N, Asanuma K, Kobayashi D, Yagihashi A, Hirata K, Torigoe T, Sato N, Watanabe N (2004) Survivin as a predictor of cis-diamminedichloroplatinum sensitivity in gastric cancer patients. Cancer Sci 95(1):44–51

    Article  PubMed  CAS  Google Scholar 

  32. Wang ZN, Xu HM, Jiang L, Zhou X, Lu C, Zhang X (2004) Expression of survivin in primary and metastatic gastric cancer cells obtained by laser capture microdissection. World J Gastroenterol 10(21):3094–3098

    PubMed  CAS  Google Scholar 

  33. Chang JL, Chen TH, Wang CF, Chiang YH, Huang YL, Wong FH, Chou CK, Chen CM (2006) Borealin/Dasra B is a cell cycle-regulated chromosomal passenger protein and its nuclear accumulation is linked to poor prognosis for human gastric cancer. Exp Cell Res 312(7):962–973

    Article  PubMed  CAS  Google Scholar 

  34. Deng H, Wu RL, Zhou HY, Huang X, Chen Y, Liu LJ (2006) Significance of Survivin and PTEN expression in full lymph node-examined gastric cancer. World J Gastroenterol 12(7):1013–1017

    PubMed  CAS  Google Scholar 

  35. Lee GH, Joo YE, Koh YS, Chung IJ, Park YK, Lee JH, Kim HS, Choi SK, Rew JS, Park CS, Kim SJ (2006) Expression of survivin in gastric cancer and its relationship with tumor angiogenesis. Eur J Gastroenterol Hepatol 18(9):957–963

    Article  PubMed  CAS  Google Scholar 

  36. Da CL, Xin Y, Zhao J, Luo XD (2009) Significance and relationship between Yes-associated protein and survivin expression in gastric carcinoma and precancerous lesions. World J Gastroenterol 15(32):4055–4061

    Article  PubMed  CAS  Google Scholar 

  37. Okayama H, Kumamoto K, Saitou K, Hayase S, Kofunato Y, Sato Y, Miyamoto K, Nakamura I, Ohki S, Sekikawa K, Takenoshita S (2009) CD44v6, MMP-7 and nuclear Cdx2 are significant biomarkers for prediction of lymph node metastasis in primary gastric cancer. Oncol Rep 22(4):745–755

    PubMed  Google Scholar 

  38. Song KY, Jung CK, Park WS, Park CH (2009) Expression of the antiapoptosis gene Survivin predicts poor prognosis of stage III gastric adenocarcinoma. Jpn J Clin Oncol 39(5):290–296

    Article  PubMed  Google Scholar 

  39. Li Y, Tan BB, Fan LQ, Zhao Q, Liu Y, Wang D (2010) Expression of COX-2, survivin in regional lymph node metastases of gastric carcinoma and the correlation with prognosis. Hepatogastroenterology 57(104):1435–1441

    PubMed  CAS  Google Scholar 

  40. Kim MA, Lee HE, Lee HS, Yang HK, Kim WH (2011) Expression of apoptosis-related proteins and its clinical implication in surgically resected gastric carcinoma. Virchows Arch 459(5):503–510

    Article  PubMed  CAS  Google Scholar 

  41. Bury J, Szumilo J, Dabrowski A, Ciechanski A, Sliwinska J, Wallner G (2012) Vascular endothelial growth factor and survivin immunostaining in gastric adenocarcinoma. Pol Przegl Chir 84(7):341–347

    PubMed  Google Scholar 

  42. Meng JR, Tang HZ, Zhou KZ, Shen WH, Guo HY (2012) TFF3 and survivin expressions associate with a lower survival rate in gastric cancer. Clin Exp Med

  43. Zheng WE, Chen H, Yuan SF, Wu LL, Zhang W, Sun HY, Chen WJ (2012) Overexpression of betaIII-tubulin and survivin associated with drug resistance to docetaxel-based chemotherapy in advanced gastric cancer. J Buon 17(2):284–290

    PubMed  Google Scholar 

  44. Piccirillo JF (1995) Purposes, problems, and proposals for progress in cancer staging. Arch Otolaryngol Head Neck Surg 121(2):145–149

    Article  PubMed  CAS  Google Scholar 

  45. Nomura M, Shitara K, Kodaira T, Hatooka S, Mizota A, Kondoh C, Yokota T, Takahari D, Ura T, Muro K (2012) Prognostic impact of the 6th and 7th American Joint Committee on Cancer TNM staging systems on esophageal cancer patients treated with chemoradiotherapy. Int J Radiat Oncol Biol Phys 82(2):946–952

    Article  PubMed  Google Scholar 

  46. Egger M, Zellweger-Zahner T, Schneider M, Junker C, Lengeler C, Antes G (1997) Language bias in randomised controlled trials published in English and German. Lancet 350(9074):326–329

    Article  PubMed  CAS  Google Scholar 

  47. Li C, Li Z, Zhu M, Zhao T, Chen L, Ji W, Chen H, Su C (2012) Clinicopathological and prognostic significance of survivin over-expression in patients with esophageal squamous cell carcinoma: a meta-analysis. PLoS One 7(9):e44764

    Article  PubMed  CAS  Google Scholar 

  48. Zhang LQ, Wang J, Jiang F, Xu L, Liu FY, Yin R (2012) Prognostic value of survivin in patients with non-small cell lung carcinoma: a systematic review with meta-analysis. PLoS One 7(3):e34100

    Article  PubMed  CAS  Google Scholar 

  49. Tu SP, Jiang XH, Lin MC, Cui JT, Yang Y, Lum CT, Zou B, Zhu YB, Jiang SH, Wong WM, Chan AO, Yuen MF, Lam SK, Kung HF, Wong BC (2003) Suppression of survivin expression inhibits in vivo tumorigenicity and angiogenesis in gastric cancer. Cancer Res 63(22):7724–7732

    PubMed  CAS  Google Scholar 

  50. Idenoue S, Hirohashi Y, Torigoe T, Sato Y, Tamura Y, Hariu H, Yamamoto M, Kurotaki T, Tsuruma T, Asanuma H, Kanaseki T, Ikeda H, Kashiwagi K, Okazaki M, Sasaki K, Sato T, Ohmura T, Hata F, Yamaguchi K, Hirata K, Sato N (2005) A potent immunogenic general cancer vaccine that targets survivin, an inhibitor of apoptosis proteins. Clin Cancer Res 11(4):1474–1482

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Andreas Krieg.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Krieg, A., Baseras, B., Tomczak, M. et al. Role of survivin as prognostic and clinicopathological marker in gastric cancer: a meta-analysis. Mol Biol Rep 40, 5501–5511 (2013). https://doi.org/10.1007/s11033-013-2650-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-013-2650-z

Keywords

Navigation