Skip to main content

Advertisement

SpringerLink
Log in

Bcl-2 expression and patient survival in gastric cancer: a systematic review of the literature with meta-analysis

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

The prognostic role of Bcl-2 in gastric cancer remains controversial. We systematically reviewed the evidence for the effect of Bcl-2 expression in gastric cancer to elucidate this issue. PubMed, EMBASE, and Web of Science were searched to identify eligible studies to evaluate the association between Bcl-2 expression and overall survival (OS) and clinicopathological features of gastric cancer. Hazard ratios (HRs) or odds ratios (ORs) with 95 % confidence interval (95 % CI) were pooled to estimate the effect. Bcl-2 expression was not significantly correlated with OS of gastric cancer patients (combined HR 0.88, 95 % CI 0.62–1.25). Subgroup analysis indicated that Bcl-2 expression had a favorable impact on OS in Asian countries (HR 0.60, 95 % CI 0.47–0.77) and cutoff value <15 % (HR 0.69, 95 % CI 0.48–0.97). Furthermore, Bcl-2 expression was significantly associated with TNM stage (OR 0.58, 95 % CI 0.41–0.80), the depth of invasion (OR 0.53, 95 % CI 0.37–0.76), and lymph node metastasis (OR 0.55, 95 % CI 0.42–0.71). Bcl-2 expression predicts less invasion and malignancy in clinicopathological features. Moreover, Bcl-2 could be a favorable prognostic marker for patients of Asian countries.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108.

    Article  PubMed  Google Scholar 

  2. Allgayer H, Heiss MM, Schildberg FW. Prognostic factors in gastric cancer. Br J Surg. 1997;84(12):1651–64.

    Article  CAS  PubMed  Google Scholar 

  3. Harrison JD, Fielding JW. Prognostic factors for gastric cancer influencing clinical practice. World J Surg. 1995;19(4):496–500.

    Article  CAS  PubMed  Google Scholar 

  4. Kim BS, Cho SW, Min SK, Lee BH. Differences in prognostic factors between early and advanced gastric cancer. Hepatogastroenterology. 2011;58(107–108):1032–40.

    PubMed  Google Scholar 

  5. Xing X, Tang YB, Yuan G, Wang Y, Wang J, Yang Y, Chen M. The prognostic value of E-cadherin in gastric cancer: a meta-analysis. Int J Cancer. 2013;132(11):2589–96. doi:10.1002/ijc.27947.

    Article  CAS  PubMed  Google Scholar 

  6. Yasui W, Hata J, Yokozaki H, Nakatani H, Ochiai A, Ito H, Tahara E. Interaction between epidermal growth factor and its receptor in progression of human gastric carcinoma. Int J Cancer. 1988;41(2):211–7.

    Article  CAS  PubMed  Google Scholar 

  7. Deveci MS, Deveci G. Prognostic value of p53 protein and MK-1 (a tumor-associated antigen) expression in gastric carcinoma. Gastric Cancer. 2007;10(2):112–6. doi:10.1007/s10120-007-0418-7.

    Article  CAS  PubMed  Google Scholar 

  8. Fondevila C, Metges JP, Fuster J, Grau JJ, Palacin A, Castells A, Volant A, Pera M. p53 and VEGF expression are independent predictors of tumour recurrence and survival following curative resection of gastric cancer. Br J Cancer. 2004;90(1):206–15. doi:10.1038/sj.bjc.6601455.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Korsmeyer SJ. Bcl-2 initiates a new category of oncogenes: regulators of cell death. Blood. 1992;80(4):879–86.

    CAS  PubMed  Google Scholar 

  10. McDonnell TJ, Troncoso P, Brisbay SM, Logothetis C, Chung LW, Hsieh JT, Tu SM, Campbell ML. Expression of the protooncogene bcl-2 in the prostate and its association with emergence of androgen-independent prostate cancer. Cancer Res. 1992;52(24):6940–4.

    CAS  PubMed  Google Scholar 

  11. Pietenpol JA, Papadopoulos N, Markowitz S, Willson JK, Kinzler KW, Vogelstein B. Paradoxical inhibition of solid tumor cell growth by bcl2. Cancer Res. 1994;54(14):3714–7.

    CAS  PubMed  Google Scholar 

  12. Ishida H, Irie K, Itoh T, Furukawa T, Tokunaga O. The prognostic significance of p53 and bcl-2 expression in lung adenocarcinoma and its correlation with Ki-67 growth fraction. Cancer. 1997;80(6):1034–45.

    Article  CAS  PubMed  Google Scholar 

  13. Yildirim M, Suren D, Goktas S, Dilli UD, Kaya C, Copuroglu R, Yildiz M, Sezer C. The predictive role of Bcl-2 expression in operable locally advanced or metastatic gastric carcinoma. J BUON. 2012;17(1):106–9.

    CAS  PubMed  Google Scholar 

  14. Saegusa M, Takano Y, Okayasu I. Bcl-2 expression and its association with cell kinetics in human gastric carcinomas and intestinal metaplasia. J Cancer Res Clin Oncol. 1995;121(6):357–63.

    Article  CAS  PubMed  Google Scholar 

  15. Nakanishi H, Ohsawa M, Naka N, Uchida A, Ochi T, Aozasa K. Immunohistochemical detection of bcl-2 and p53 proteins and apoptosis in soft tissue sarcoma: their correlations with prognosis. Oncology. 1997;54(3):238–44.

    Article  CAS  PubMed  Google Scholar 

  16. Lee HK, Lee HS, Yang HK, Kim WH, Lee KU, Choe KJ, Kim JP. Prognostic significance of Bcl-2 and p53 expression in gastric cancer. Int J Colorectal Dis. 2003;18(6):518–25. doi:10.1007/s00384-003-0491-2.

    Article  PubMed  Google Scholar 

  17. Tsamandas AC, Kardamakis D, Tsiamalos P, Liava A, Tzelepi V, Vassiliou V, Petsas T, Vagenas K, Zolota V, Scopa CD. The potential role of Bcl-2 expression, apoptosis and cell proliferation (Ki-67 expression) in cases of gastric carcinoma and correlation with classic prognostic factors and patient outcome. Anticancer Res. 2009;29(2):703–9.

    PubMed  Google Scholar 

  18. Wiksten JP, Lundin J, Nordling S, Kokkola A, Haglund C. Comparison of the prognostic value of a panel of tissue tumor markers and established clinicopathological factors in patients with gastric cancer. Anticancer Res. 2008;28(4C):2279–87.

    PubMed  Google Scholar 

  19. Zafirellis K, Karameris A, Milingos N, Androulakis G. Molecular markers in gastric cancer: can p53 and bcl-2 protein expressions be used as prognostic factors? Anticancer Res. 2005;25(5):3629–36.

    CAS  PubMed  Google Scholar 

  20. Liu X, Cai H, Huang H, Long Z, Shi Y, Wang Y. The prognostic significance of apoptosis-related biological markers in Chinese gastric cancer patients. PLoS One. 2011;6(12):e29670. doi:10.1371/journal.pone.0029670.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Inada T, Kikuyama S, Ichikawa A, Igarashi S, Ogata Y. Bcl-2 expression as a prognostic factor of survival of gastric carcinoma. Anticancer Res. 1998;18(3B):2003–10.

    CAS  PubMed  Google Scholar 

  22. Forones NM, Kawamura KY, Segreto HR, Artigiani Neto R, Focchi GR, Oshima CT. Expression of COX-2 in stomach carcinogenesis. J Gastrointest Cancer. 2008;39(1–4):4–10. doi:10.1007/s12029-008-9039-6.

    Article  CAS  PubMed  Google Scholar 

  23. Sezer C, Yildirim M, Yildiz M, Sezgin A, Donem Dilli U, Goktas S, Bulbuller N. Prognostic significance of biological apoptosis factors in gastric cancer. J BUON. 2013;18(1):138–46.

    CAS  PubMed  Google Scholar 

  24. Muller W, Schneiders A, Hommel G, Gabbert HE. Prognostic value of bcl-2 expression in gastric cancer. Anticancer Res. 1998;18(6B):4699–704.

    CAS  PubMed  Google Scholar 

  25. Kopp R, Diebold J, Dreier I, Cramer C, Glas J, Baretton G, Jauch KW. Prognostic relevance of p53 and bcl-2 immunoreactivity for early invasive pT1/pT2 gastric carcinomas: indicators for limited gastric resections? Surg Endosc. 2005;19(11):1507–12. doi:10.1007/s00464-005-0043-7.

    Article  CAS  PubMed  Google Scholar 

  26. Aizawa K, Ueki K, Suzuki S, Yabusaki H, Kanda T, Nishimaki T, Suzuki T, Hatakeyama K. Apoptosis and Bbcl-2 expression in gastric carcinomas: correlation with clinicopathological variables, p53 expression, cell proliferation and prognosis. Int J Oncol. 1999;14(1):85–91.

    CAS  PubMed  Google Scholar 

  27. Nordmann AJ, Kasenda B, Briel M. Meta-analyses: what they can and cannot do. Swiss Med Wkly. 2012;142:w13518. doi:10.4414/smw.2012.13518.

    PubMed  Google Scholar 

  28. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097. doi:10.1371/journal.pmed.1000097.

    Article  PubMed Central  PubMed  Google Scholar 

  29. Steels E, Paesmans M, Berghmans T, Branle F, Lemaitre F, Mascaux C, Meert AP, Vallot F, Lafitte JJ, Sculier JP. 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. 2001;18(4):705–19.

    Article  CAS  PubMed  Google Scholar 

  30. McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM. REporting recommendations for tumour MARKer prognostic studies (REMARK). Br J Cancer. 2005;93(4):387–91. doi:10.1038/sj.bjc.6602678.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med. 1998;17(24):2815–34.

    Article  CAS  PubMed  Google Scholar 

  32. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Tsujimoto Y, Ikegaki N, Croce CM. Characterization of the protein product of bcl-2, the gene involved in human follicular lymphoma. Oncogene. 1987;2(1):3–7.

    CAS  PubMed  Google Scholar 

  34. Diebold J, Baretton G, Felchner M, Meier W, Dopfer K, Schmidt M, Lohrs U. Bcl-2 expression, p53 accumulation, and apoptosis in ovarian carcinomas. Am J Clin Pathol. 1996;105(3):341–9.

    CAS  PubMed  Google Scholar 

  35. Pezzella F, Turley H, Kuzu I, Tungekar MF, Dunnill MS, Pierce CB, Harris A, Gatter KC, Mason DY. Bcl-2 protein in non-small-cell lung carcinoma. N Engl J Med. 1993;329(10):690–4. doi:10.1056/nejm199309023291003.

    Article  CAS  PubMed  Google Scholar 

  36. Bubendorf L, Sauter G, Moch H, Jordan P, Blochlinger A, Gasser TC, Mihatsch MJ. Prognostic significance of Bcl-2 in clinically localized prostate cancer. Am J Pathol. 1996;148(5):1557–65.

    CAS  PubMed Central  PubMed  Google Scholar 

  37. Saegusa M, Takano Y, Hashimura M, Shoji Y, Okayasu I. The possible role of bcl-2 expression in the progression of tumors of the uterine cervix. Cancer. 1995;76(11):2297–303.

    Article  CAS  PubMed  Google Scholar 

  38. Karamitopoulou E, Perentes E, Tolnay M, Probst A. Prognostic significance of MIB-1, p53, and bcl-2 immunoreactivity in meningiomas. Hum Pathol. 1998;29(2):140–5.

    Article  CAS  PubMed  Google Scholar 

  39. Koshida Y, Saegusa M, Okayasu I. Apoptosis, cell proliferation and expression of Bcl-2 and Bax in gastric carcinomas: immunohistochemical and clinicopathological study. Br J Cancer. 1997;75(3):367–73.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Tsamandas AC, Kardamakis D, Petsas T, Zolota V, Vassiliou V, Matatsoris T, Kalofonos H, Vagianos CE, Scopa CD. Bcl-2, bax and p53 expression in rectal adenocarcinoma. Correlation with classic pathologic prognostic factors and patients’ outcome. In Vivo. 2007;21(1):113–8.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank all colleagues from the Department of General Surgery, Chinese People’s Liberation Army General Hospital, for their help and supports in this study.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Medical Center, Tsinghua University, Beijing, 100084, China

    Haidong Cheng

  2. The Affiliated People’s Hospital of Inner Mongolia Medical University, Hohhot, 010042, China

    Xiumei Wang

  3. Department of General Surgery, Chinese People’s Liberation Army General Hospital, 28 Fuxing Road, Beijing, 100853, China

    Tao Li & Lin Chen

Authors
  1. Haidong Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiumei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tao Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lin Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lin Chen.

Additional information

Haidong Cheng and Xiumei Wang have contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cheng, H., Wang, X., Li, T. et al. Bcl-2 expression and patient survival in gastric cancer: a systematic review of the literature with meta-analysis. Med Oncol 32, 389 (2015). https://doi.org/10.1007/s12032-014-0389-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-014-0389-6

Keywords

Search

Navigation