Skip to main content

Advertisement

Log in

High level of serum AMBP is associated with poor response to paclitaxel–capecitabine chemotherapy in advanced gastric cancer patients

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

Abstract

Gastric cancer is one of the most common human cancers and ranks the second in the global cancer-related mortality. The clinical outcome of patients with advanced gastric cancer (AGC) is markedly dependent on their response to the chemotherapy. Paclitaxel plus capecitabine, as a first-line regimen, is widely administrated in AGC patients, but more than a half of the patients have a poor response, possibly due to their resistance to the treatment. Therefore, it is important to identify potential responders to improve the efficacy of the chemotherapy. In the present study, we used an isobaric tag approach for relative and absolute quantification combined with ESI-QUAD-TOF/MS to identify potential predictive biomarkers for the chemotherapy. We found 211 serum proteins, and confirmed 17 candidates that were differentially present in the progression of disease (PD) group and the partial response (PR) group to the treatment of paclitaxel plus capecitabine. In further validation of the 17 candidates in the set of 12 PD and 12 PR AGC patients, we identified a higher level of AMBP (Alpha-1-Microglobulin/Bikunin Precursor) in the sera of PD patients than of the PR patients assayed by ELISA (9.13 ± 0.45 vs. 8.11 ± 0.26 μg/mL, p = 0.06) and by the Western blotting (relative gray value 396.4 ± 39.1 vs. 275.0 ± 34.76, p = 0.03), respectively. The receiver operating characteristics curve showed 75 % sensitivity and 75 % specificity of AMBP in AGC patients treated with the chemotherapy. Our data indicated that the high level of serum AMBP could predict the poor response of the AGC patients treated with the paclitaxel–capecitabine chemotherapy, which could be used as a potential biomarker to identify patients who would benefit from this chemotherapeutic regimen.

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
Fig. 4

Similar content being viewed by others

References

  1. Nagini S. Carcinoma of the stomach: a review of epidemiology, pathogenesis, molecular genetics and chemoprevention. World J Gastrointest Oncol. 2012;4(7):156–69.

    Article  PubMed Central  PubMed  Google Scholar 

  2. Guggenheim DE, Shah MA. Gastric cancer epidemiology and risk factors. J Surg Oncol. 2013;107(3):230–6.

    Article  PubMed  Google Scholar 

  3. Lustosa SA, Saconato H, Atallah AN, Lopes Filho Gde J, Matos D. Impact of extended lymphadenectomy on morbidity, mortality, recurrence and 5-year survival after gastrectomy for cancer. Meta-analysis of randomized clinical trials. Acta Cir Bras. 2008;23(6):520–30.

    Article  PubMed  Google Scholar 

  4. Kang HJ, Chang HM, Kim TW, Ryu MH, Sohn HJ, Yook JH, et al. A phase II study of paclitaxel and capecitabine as a first-line combination chemotherapy for advanced gastric cancer. Br J Cancer. 2008;98(2):316–22.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Deng L, Su T, Leng A, Zhang X, Xu M, Yan L, et al. Upregulation of soluble resistance-related calcium-binding protein (sorcin) in gastric cancer. Med Oncol. 2010;27(4):1102–8.

    Article  CAS  PubMed  Google Scholar 

  6. Liang S, Xu Z, Xu X, Zhao X, Huang C, Wei Y. Quantitative proteomics for cancer biomarker discovery. Comb Chem High Throughput Screen. 2012;15(3):221–31.

    Article  CAS  PubMed  Google Scholar 

  7. Wang L, Chen S, Zhang M, Li N, Chen Y, Su W, et al. Legumain: a biomarker for diagnosis and prognosis of human ovarian cancer. J Cell Biochem. 2012;113(8):2679–86.

    Article  CAS  PubMed  Google Scholar 

  8. Zhang X, Xiao Z, Liu X, Du L, Wang L, Wang S, et al. The potential role of ORM2 in the development of colorectal cancer. PLoS One. 2012;7(2):e31868.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Chen CL, Lin TS, Tsai CH, Wu CC, Chung T, Chien KY, et al. Identification of potential bladder cancer markers in urine by abundant-protein depletion coupled with quantitative proteomics. J Proteomics. 2013;85:28–43.

    Article  CAS  PubMed  Google Scholar 

  10. Marimuthu A, Chavan S, Sathe G, Sahasrabuddhe NA, Srikanth SM, Renuse S, et al. Identification of head and neck squamous cell carcinoma biomarker candidates through proteomic analysis of cancer cell secretome. Biochim Biophys Acta. 2013.

  11. Tonack S, Jenkinson C, Cox T, Elliott V, Jenkins RE, Kitteringham NR, et al. iTRAQ reveals candidate pancreatic cancer serum biomarkers: influence of obstructive jaundice on their performance. Br J Cancer. 2013;108(9):1846–53.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92(3):205–16.

    Article  CAS  PubMed  Google Scholar 

  13. Elias JE, Gygi SP. Target-decoy search strategy for increased confidence in large-scale protein identifications by mass spectrometry. Nat Methods. 2007;4(3):207–14.

    Article  CAS  PubMed  Google Scholar 

  14. Chen Z, Wen B, Wang Q, Tong W, Guo J, Bai X, et al. Quantitative proteomics reveals the temperature-dependent proteins encoded by a series of cluster genes in thermoanaerobacter tengcongensis. Mol Cell Proteomics. 2013;12(8):2266–77.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Wong R, Cunningham D. Optimising treatment regimens for the management of advanced gastric cancer. Ann Oncol. 2009;20(4):605–8.

    Article  CAS  PubMed  Google Scholar 

  16. Fedorenko IV, Paraiso KH, Smalley KS. Acquired and intrinsic BRAF inhibitor resistance in BRAF V600E mutant melanoma. Biochem Pharmacol. 2011;82(3):201–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Shekhar MP. Drug resistance: challenges to effective therapy. Curr Cancer Drug Targets. 2011;11(5):613–23.

    Article  CAS  PubMed  Google Scholar 

  18. Mackenzie M, Spithoff K, Jonker D. Systemic therapy for advanced gastric cancer: a clinical practice guideline. Curr Oncol. 2011;18(4):e202–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Fujii M, Kochi M, Takayama T. Recent advances in chemotherapy for advanced gastric cancer in Japan. Surg Today. 2010;40(4):295–300.

    Article  CAS  PubMed  Google Scholar 

  20. Zhang D, Fan D. New insights into the mechanisms of gastric cancer multidrug resistance and future perspectives. Future Oncol. 2010;6(4):527–37.

    Article  CAS  PubMed  Google Scholar 

  21. Ichikawa W, Sasaki Y. Correlation between tumor response to first-line chemotherapy and prognosis in advanced gastric cancer patients. Ann Oncol. 2006;17(11):1665–72.

    Article  CAS  PubMed  Google Scholar 

  22. Kodera Y, Ito Y, Ohashi N, Nakayama G, Koike M, Fujiwara M, et al. Impact of clinical response to first-line chemotherapy on gastric cancer patients treated with second-line and third-line chemotherapy. Hepatogastroenterology. 2011;58(107–108):1041–5.

    PubMed  Google Scholar 

  23. Gorg A, Drews O, Luck C, Weiland F, Weiss W. 2-DE with IPGs. Electrophoresis. 2009;30(Suppl 1):S122–32.

    Article  PubMed  Google Scholar 

  24. Weiss W, Gorg A. Sample solublization buffers for two-dimensional electrophoresis. Methods Mol Biol. 2008;424:35–42.

    Article  CAS  PubMed  Google Scholar 

  25. Guo T, Gan CS, Zhang H, Zhu Y, Kon OL, Sze SK. Hybridization of pulsed-Q dissociation and collision-activated dissociation in linear ion trap mass spectrometer for iTRAQ quantitation. J Proteome Res. 2008;7(11):4831–40.

    Article  CAS  PubMed  Google Scholar 

  26. Akerstrom B, Logdberg L, Berggard T, Osmark P, Lindqvist A. alpha(1)-Microglobulin: a yellow-brown lipocalin. Biochim Biophys Acta. 2000;1482(1–2):172–84.

    Article  CAS  PubMed  Google Scholar 

  27. Olsson MG, Allhorn M, Bulow L, Hansson SR, Ley D, Olsson ML, et al. Pathological conditions involving extracellular hemoglobin: molecular mechanisms, clinical significance, and novel therapeutic opportunities for alpha(1)-microglobulin. Antioxid Redox Signal. 2012;17(5):813–46.

    Article  CAS  PubMed  Google Scholar 

  28. Fries E, Blom AM. Bikunin–not just a plasma proteinase inhibitor. Int J Biochem Cell Biol. 2000;32(2):125–37.

    Article  CAS  PubMed  Google Scholar 

  29. Chong PK, Lee H, Loh MC, Choong LY, Lin Q, So JB, et al. Upregulation of plasma C9 protein in gastric cancer patients. Proteomics. 2010;10(18):3210–21.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Chong PK, Lee H, Zhou J, Liu SC, Loh MC, Wang TT, et al. ITIH3 is a potential biomarker for early detection of gastric cancer. J Proteome Res. 2010;9(7):3671–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Uhlen M, Oksvold P, Fagerberg L, et al. Towards a knowledge-based human protein atlas. Nat Biotechnol. 2010;28:1248–50. doi:www.nature.com/nbt/journal/v28/n12/abs/nbt1210-1248.html.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by National Basic Research Program of China (No. 2010CB5529303) and Beijing Municipal Science and Technology Commission Program (No. Z11110706730000).

Conflict of interest

The authors have no conflict of interest concerning this study.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Lin Shen or Chengchao Shou.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 182 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huang, H., Han, Y., Gao, J. et al. High level of serum AMBP is associated with poor response to paclitaxel–capecitabine chemotherapy in advanced gastric cancer patients. Med Oncol 30, 748 (2013). https://doi.org/10.1007/s12032-013-0748-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-013-0748-8

Keywords

Navigation