Skip to main content

Overexpression of 3-phosphoinositide-dependent protein kinase-1 is associated with prognosis of gastric carcinoma

Tumor Biology volume 37, pages 2333–2339 (2016)Cite this article

Abstract

This study investigated the correlation between the expression of 3-phosphoinositide-dependent protein kinase-1 (PDK1) and the prognosis of gastric carcinoma patients. A total of 156 paired tumor and matched normal samples were collected from patients of gastric carcinoma who underwent surgical resection. The expression of PDK1 was analyzed by real-time quantitative PCR and immunohistochemistry method. Potential correlation between PDK1 protein expression and the clinicopathological characteristics was determined by chi-square test and Spearman correlation analysis. The influence of PDK1 expression on 5-year survival rate and survival length was determined by Kaplan–Meier analysis. The expression of PDK1 mRNA and protein were significantly higher in tumor samples comparing to those in adjacent normal samples (paired t test, P = 0.007). Immunohistochemical staining results indicated that PDK1 protein level was positively correlated with infiltration (P = 0.006). However, no associations with age, sex, clinical stage, lymph node metastasis, and distant metastasis were observed (P > 0.05). The 5-year survival rate was 20.1 and 63.4 % of the patients with high and low expression level of PDK1, respectively (P < 0.05). The median survival length was 32.5 months (95 % CI 22.8–37.6) for patients with high level of PDK1 and 63.1 months (95 % CI 52.3–64.7) for patients with low level of PDK1 (×2 = 20.153, P < 0.05). Kaplan–Meier survival curves demonstrated that elevated expression of PDK1 was an independent negative prognostic factor of gastric carcinoma (P<0.05). Our study indicated that PDK1 might serve as a candidate pro-oncogene and a potential prognostic biomarker for gastric carcinoma.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, et al. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.

    Article  PubMed  Google Scholar 

  2. Arsenic R. Immunohistochemical analysis of PDK1 expression in breast cancer. Diagn Pathol. 2014;9:82.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Lu CW, Lin SC, Chien CW, Lee CT, Lin BW, et al. Overexpression of pyruvate dehydrogenase kinase 3 increases drug resistance and early recurrence in colon cancer. Am J Pathol. 2011;179:1405–14.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. Galgano MT, Conaway M, Spencer AM, Paschal BM, Frierson Jr HF. PRK1 distribution in normal tissues and carcinomas: overexpression and activation in ovarian serous carcinoma. Hum Pathol. 2009;40:1434–40.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. Bayascas JR. PDK1: the major transducer of PI 3-kinase actions. Curr Top Microbiol Immunol. 2010;346:9–29.

    CAS  PubMed  Google Scholar 

  6. Williams MR, Arthur JS, Balendran A, van der Kaay J, Poli V, Cohen P, et al. The role of 3-phosphoinositide-dependent protein kinase 1 in activating AGC kinases defined in embryonic stem cells. Curr Biol. 2000;10(8):439–48.

    CAS  Article  PubMed  Google Scholar 

  7. Cantley LC. The phosphoinositide 3-kinase pathway. Science. 2002;296(5573):1655–7.

    CAS  Article  PubMed  Google Scholar 

  8. Willems L, Tamburini J, Chapuis N, Lacombe C, Mayeux P, Bouscary D. PI3K and mTOR signaling pathways in cancer: new data on targeted therapies. Curr Oncol Rep. 2012;14(2):129–38.

    CAS  Article  PubMed  Google Scholar 

  9. Nam SY, Lee HS, Jung G-A, Choi J, Cho SJ, Kim MK, et al. Akt/PKB activation in gastric carcinomas correlates with clinicopathologic variables and prognosis. APMIS. 2003;111(12):1105–13.

    CAS  Article  PubMed  Google Scholar 

  10. Manning BD, Cantley LC. AKT/PKB signaling: navigating downstream. Cell. 2007;129(7):1261–74.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. Zetter BR. Angiogenesis and tumor metastasis. Annu Rev Med. 1998;49:407–24.

    CAS  Article  PubMed  Google Scholar 

  12. Zhou XD, Chen HX, Guan RN, Lei YP, Shu X, Zhu Y, et al. Protein kinase B phosphorylation correlates with vascular endothelial growth factor A and microvessel density in gastric adenocarcinoma. J Int Med Res. 2012;40(6):2124–34.

    CAS  Article  PubMed  Google Scholar 

  13. Sheng S, Qiao M, Pardee AB. Metastasis and AKT activation. JCell Physiol. 2009;218(3):451–4.

    CAS  Article  Google Scholar 

  14. Cinti C, Vindigni C, Zamparelli A, La Sala D, Epistolato MC, Marrelli D, et al. Activated Akt as an indicator of prognosis in gastric cancer. Virchows Arch. 2008;453(5):449–55.

    CAS  Article  PubMed  Google Scholar 

  15. Isakoff SJ, Engelman JA, Irie HY, Luo J, Brachmann SM, Pearline RV, et al. Breast cancer-associated PIK3CA mutations are oncogenic in mammary epithelial cells. Cancer Res. 2005;65(23):10992–1000.

    CAS  Article  PubMed  Google Scholar 

  16. Zhou BP, Hu MC, Miller SA, Yu Z, Xia W, Lin SY, et al. HER-2/neu blocks tumor necrosis factor-induced apoptosis via the Akt/NF-kappaB pathway. J Biol Chem. 2000;275(11):8027–31.

    CAS  Article  PubMed  Google Scholar 

  17. Maurer M, Su T, Saal LH, Koujak S, Hopkins BD, Barkley CR, et al. PDK1 potentiates upstream lesions on the PI3K pathway in breast carcinoma. Cancer Res. 2009;69(15):6299–306.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  18. Tan J, Li Z, Lee PL, Guan P, Aau MY, Lee ST, et al. PDK1 signaling toward PLK1-MYC activation confers oncogenic transformation, tumor-initiating cell activation, and resistance to mTOR-targeted therapy. Cancer Discov. 2013;3(10):1156–71.

    CAS  Article  PubMed  Google Scholar 

Download references

Author information

Affiliations

  1. Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Science, Beijing, 100021, China

    Xiaofeng Bai, Peng Li, Yibin Xie, Chunguang Guo, Yuemin Sun, Quan Xu & Dongbing Zhao

Authors
  1. Xiaofeng Bai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peng Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yibin Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chunguang Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yuemin Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Quan Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Dongbing Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dongbing Zhao.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Bai, X., Li, P., Xie, Y. et al. Overexpression of 3-phosphoinositide-dependent protein kinase-1 is associated with prognosis of gastric carcinoma. Tumor Biol. 37, 2333–2339 (2016). https://doi.org/10.1007/s13277-015-4024-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-015-4024-8

Keywords

  • Gastric carcinoma
  • 3-Phosphoinositide-dependent protein kinase-1 (PDK1)
  • Prognosis
  • Infiltration