Skip to main content

Advertisement

SpringerLink
Log in

NS5ATP9 mRNA levels in peripheral blood mononuclear cells predict prognosis in patients with gastric cancer

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

Abstract

The prognosis for gastric cancer is poor; therefore, there is urgent need for the development of novel, especially noninvasive surrogate biomarkers. NS5ATP9 is significantly overexpressed in gastric cancer tissues, and altered NS5ATP9 expression in human gastric cancer is associated with tumor recurrence. This study aimed to determine whether a correlation exists between NS5ATP9 mRNA levels in peripheral blood mononuclear cells (PBMCs) and gastric cancer prognosis in patients. NS5ATP9 mRNA levels were assessed by real-time RT-PCR in PBMC samples obtained from 207 gastric cancer patients, 47 patients with benign gastric lesions, and 78 healthy individuals. In addition, NS5ATP9 protein expression was evaluated by Western blot in PBMC samples from 30 gastric cancer patients and 30 healthy individuals, chosen randomly. Finally, clinicopathological data and survival of all gastric cancer patients were collected and analyzed. NS5ATP9 in PBMCs from gastric cancer patients was significantly upregulated both at mRNA and protein levels. Interestingly, NS5ATP9 mRNA overexpression in PBMCs was significantly associated with poor disease-free survival and overall survival of cancer patients, but not with tumor recurrence. Multivariate analysis showed NS5ATP9 mRNA levels and tumor lymph node metastasis were independent correlation with 3-year survival rate. Importantly, the diagnostic sensitivity and specificity (70.6 and 79.5 %, respectively) were higher for NS5ATP9 mRNA in PBMCs compared with the serum tumor markers CEA (45.0 and 84.6 %, respectively) and CA19-9 (61.5 and 69.2 %, respectively). These findings suggested that NS5ATP9 mRNA levels in PBMCs can be used for prognosis in gastric cancer patients.

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. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.

    Article  PubMed  Google Scholar 

  2. Bosman FT, Carneiro F, Hruban RH, Theise ND. WHO classification of tumours of the digestive system. vol Ed. 4. World Health Organization; 2010.

  3. Pietrantonio F, De Braud F, Da Prat V, Perrone F, Pierotti MA, Gariboldi M, et al. A Review on Biomarkers for Prediction of Treatment Outcome in Gastric Cancer. Anticancer Res. 2013;33(4):1257–66.

    CAS  PubMed  Google Scholar 

  4. Simpson F, Lammerts van Bueren K, Butterfield N, Bennetts JS, Bowles J, Adolphe C, et al. The PCNA-associated factor KIAA0101/p15PAF binds the potential tumor suppressor product p33ING1b. Exp Cell Res. 2006;312(1):73–85.

    Article  CAS  PubMed  Google Scholar 

  5. Yu P, Huang B, Shen M, Lau C, Chan E, Michel J, et al. p15 (PAF), a novel PCNA associated factor with increased expression in tumor tissues. Oncogene. 2001;20(4):484.

    Article  CAS  PubMed  Google Scholar 

  6. Petroziello J, Yamane A, Westendorf L, Thompson M, McDonagh C, Cerveny C, et al. Suppression subtractive hybridization and expression profiling identifies a unique set of genes overexpressed in non-small-cell lung cancer. Oncogene. 2004;23(46):7734–45.

    Article  CAS  PubMed  Google Scholar 

  7. Mizutani K, Onda M, Asaka S, Akaishi J, Miyamoto S, Yoshida A, et al. Overexpressed in anaplastic thyroid carcinoma‐1 (OEATC‐1) as a novel gene responsible for anaplastic thyroid carcinoma. Cancer. 2005;103(9):1785–90.

    Article  CAS  PubMed  Google Scholar 

  8. Yuan RH, Jeng YM, Pan HW, Hu FC, Lai PL, Lee PH, et al. Overexpression of KIAA0101 predicts high stage, early tumor recurrence, and poor prognosis of hepatocellular carcinoma. Clin Cancer Res. 2007;13(18):5368–76.

    Article  CAS  PubMed  Google Scholar 

  9. Kais Z, Barsky SH, Mathsyaraja H, Zha A, Ransburgh DJ, He G, et al. KIAA0101 interacts with BRCA1 and regulates centrosome number. Mol Cancer Res. 2011;9(8):1091–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Kato T, Daigo Y, Aragaki M, Ishikawa K, Sato M, Kaji M. Overexpression of KIAA0101 predicts poor prognosis in primary lung cancer patients. Lung Cancer. 2012;75(1):110–8.

    Article  PubMed  Google Scholar 

  11. Jain M, Zhang L, Patterson EE, Kebebew E. KIAA0101 is overexpressed, and promotes growth and invasion in adrenal cancer. PLoS ONE. 2011;6(11):e26866.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Hosokawa M, Takehara A, Matsuda K, Eguchi H, Ohigashi H, Ishikawa O, et al. Oncogenic role of KIAA0101 interacting with proliferating cell nuclear antigen in pancreatic cancer. Cancer Res. 2007;67(6):2568–76.

    Article  CAS  PubMed  Google Scholar 

  13. Zhu K, Diao D, Dang C, Shi L, Wang J, Yan R et al. Elevated KIAA0101 expression is a marker of recurrence in human gastric cancer. Cancer Science. 2013.

  14. Liew C–C, Ma J, Tang H-C, Zheng R, Dempsey AA. The peripheral blood transcriptome dynamically reflects system wide biology: a potential diagnostic tool. J Lab Clin Med. 2006;147(3):126–32.

    Article  CAS  PubMed  Google Scholar 

  15. Manoel-Caetano FS, Xavier DJ, Evangelista AF, Takahashi P, Collares CV, Puthier D et al. Gene expression profiles displayed by peripheral blood mononuclear cells from patients with type 2 diabetes mellitus focusing on biological processes implicated on the pathogenesis of the disease. Gene. 2012.

  16. Sun C-J, Zhang L, Zhang W-Y. Gene expression profiling of maternal blood in early onset severe preeclampsia: identification of novel biomarkers. J Perinat Med. 2009;37(6):609–16.

    Article  CAS  PubMed  Google Scholar 

  17. Edwards CJ, Feldman JL, Beech J, Shields KM, Stover JA, Trepicchio WL, et al. Molecular profile of peripheral blood mononuclear cells from patients with rheumatoid arthritis. Mol Med. 2007;13(1–2):40.

    CAS  PubMed Central  PubMed  Google Scholar 

  18. Bluth M, Lin Y-y, Zhang H, Viterbo D, Zenilman M. Use of gene expression profiles in cells of peripheral blood to identify new molecular markers of acute pancreatitis. Archives of Surgery. 2008;143(3):227.

  19. Whitney AR, Diehn M, Popper SJ, Alizadeh AA, Boldrick JC, Relman DA, et al. Individuality and variation in gene expression patterns in human blood. Proc Natl Acad Sci. 2003;100(4):1896–901.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Twine NC, Stover JA, Marshall B, Dukart G, Hidalgo M, Stadler W, et al. Disease-associated expression profiles in peripheral blood mononuclear cells from patients with advanced renal cell carcinoma. Cancer Res. 2003;63(18):6069–75.

    CAS  PubMed  Google Scholar 

  21. Edge SB BD, Compton CC, Fritz AG, Greene FL, Trotti A, editors, editor. AJCC cancer staging manual (7th ed). New York: NY: Springer; 2010.

  22. Prelich G, Tan C-K, Kostura M, Mathews MB, So AG, Downey KM, et al. Functional identity of proliferating cell nuclear antigen and a DNA polymerase-δ auxiliary protein. Nature. 1987;326(6112):517–20.

    Article  CAS  PubMed  Google Scholar 

  23. Zhang Z, Shibahara K-i, Stillman B. PCNA connects DNA replication to epigenetic inheritance in yeast. Nature. 2000;408(6809):221-5.

  24. Cheung K-J, Mitchell D, Lin P, Li G. The tumor suppressor candidate p33ING1 mediates repair of UV-damaged DNA. Cancer Res. 2001;61(13):4974–7.

    CAS  PubMed  Google Scholar 

  25. Li R, Waga S, Hannon GJ, Beach D, Stillman B. Differential effects by the p21 CDK inhibitor on PCNA-dependent DNA replication and repair. Nature. 1994;371(6497):534–7.

    Article  CAS  PubMed  Google Scholar 

  26. Chang C-N, Feng M-J, Chen Y-L, Yuan R-H, Jeng Y-M. p15PAF Is an Rb/E2F-Regulated S-Phase Protein Essential for DNA Synthesis and Cell Cycle Progression. PLoS ONE. 2013;8(4):e61196.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Williams MA, Newland AC, Kelsey SM. Potential for Monocyte-Mediated Immunotherapy ring Infection and Malignancy. Part I: Apoptosis Induction and Cytotoxic Mechanisms. Leukemia & lymphoma. 1999;34(1-2):1-23.

  28. Sakai Y, Honda M, Fujinaga H, Tatsumi I, Mizukoshi E, Nakamoto Y, et al. Common transcriptional signature of tumor-infiltrating mononuclear inflammatory cells and peripheral blood mononuclear cells in hepatocellular carcinoma patients. Cancer Res. 2008;68(24):10267–79.

    Article  CAS  PubMed  Google Scholar 

  29. Kitkumthorn N, Tuangsintanakul T, Rattanatanyong P, Tiwawech D, Mutirangura A. LINE-1 methylation in the peripheral blood mononuclear cells of cancer patients. Clin Chim Acta. 2012;413(9):869–74.

    Article  CAS  PubMed  Google Scholar 

  30. Baine MJ, Chakraborty S, Smith LM, Mallya K, Sasson AR, Brand RE, et al. Transcriptional profiling of peripheral blood mononuclear cells in pancreatic cancer patients identifies novel genes with potential diagnostic utility. PLoS ONE. 2011;6(2):e17014.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Zhu M-C, Xu Y-J, Zou X, Yan F. Down-regulation of HLA-A mRNA in peripheral blood mononuclear cell of colorectal cancer. Int J Colorectal Dis. 2012;27(1):31–6.

    Article  PubMed  Google Scholar 

  32. Pantel K, Brakenhoff RH, Brandt B. Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nat Rev Cancer. 2008;8(5):329–40.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The present study was supported by grants from the National Natural Scientific Foundation of China (#81001089 to K.L. #81370069 to K.L. #81000728 to L.S.).

Ethical standards

This work has been carried out in accordance with the Declaration of Helsinki (2010) of the World Medical Association. This study was approved ethically by First Affiliated Hospital of Xi’an Jiaotong University. All patients provided informed written consent.

Conflict of interest

The authors have declared that no competing interests exist.

Author information

Authors and Affiliations

  1. Department of Surgical Oncology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, China

    Dawei Yuan, Kun Zhu, Chengxue Dang, Rong Yan & Kang Li

  2. Department of Genetics and Molecular Biology, Medical School of Xi’an Jiaotong University, Xi’an, 710061, China

    Yuewen Zheng

  3. Department of Infectious Diseases, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, China

    Lei Shi

Authors
  1. Dawei Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kun Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chengxue Dang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuewen Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rong Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lei Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kang Li.

Additional information

Dawei Yuan and Kun Zhu 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

Yuan, D., Zhu, K., Dang, C. et al. NS5ATP9 mRNA levels in peripheral blood mononuclear cells predict prognosis in patients with gastric cancer. Med Oncol 31, 106 (2014). https://doi.org/10.1007/s12032-014-0106-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-014-0106-5

Keywords

Search

Navigation