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Article

Clinical implications of progranulin in gastric cancer and its regulation via a positive feedback loop involving AKT and ERK signaling pathways

  • Authors:
    • Dong Yang
    • Ruidong Li
    • Huili Wang
    • Junye Wang
    • Lei Han
    • Lihua Pan
    • Xueqin Li
    • Qingli Kong
    • Guijuan Wang
    • Xiujun Su
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, Affiliated Hospital of Jining Medical University, Jining, Shandong 272029, P.R. China
  • Pages: 9685-9691
    |
    Published online on: October 17, 2017
       https://doi.org/10.3892/mmr.2017.7796
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Abstract

In previous years, progranulin (PGRN) has attracted increasing attention due to its oncogenic roles in several types of tumor. However, the clinical relevance of PGRN in gastric cancer remains to be elucidated. In the present study, 120 retrospective tissue samples were obtained from patients with primary gastric cancer, and the expression of PGRN was detected using immunohistochemistry. The results showed that 71 cases exhibited a high expression of PGRN, which was markedly higher than the 49 cases with a low expression of PGRN. Subsequent χ2 analysis confirmed for the first time, to the best of our knowledge, that a high level of PGRN was positively correlated with lymph node metastasis (P=0.048), lymphatic invasion (P=0.018) and advanced clinical stage (P=0.027). Survival analysis showed that PGRN was positively correlated with poorer overall survival (OS; P=0.0043) and progression‑free survival (PFS; P=0.0022). Univariate and multivariate Cox regression analysis showed that PGRN and clinical stage had a significant effect on the OS and PFS of the patients with gastric cancer. In addition, cell experiments confirmed that extracellular PGRN promoted the intracellular expression of PGRN in a concentration‑dependent manner in gastric cancer cells. The AKT and extracellular signal‑regulated kinase signaling pathways were involved in the upregulation of intracellular PGRN induced by extracellular PGRN in MKN‑45 and MGC‑803 gastric cancer cells. Taken together, the results of the present study suggested that PGRN may be important in the progression and prognosis of gastric cancer, and that the expression of PGRN was regulated in a positive feedback loop. These findings enhance current knowledge regarding PGRN in tumors.
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1 

Vohlonen I, Pukkala E, Malila N, Härkönen M, Hakama M, Koistinen V and Sipponen P: Risk of gastric cancer in Helicobacter pylori infection in a 15-year follow-up. Scand J Gastroenterol. 51:1159–1164. 2016. View Article : Google Scholar : PubMed/NCBI

2 

Hafez NH and Tahoun NS: Expression of cyclooxygenase 2 and vascular endothelial growth factor in gastric carcinoma: Relationship with clinicopathological parameters. J Egypt Natl Canc Inst. 28:149–156. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Li P, Sun D, Li X, He Y, Li W, Zhao J, Wang Y, Wang H and Xin Y: Elevated expression of Nodal and YAP1 is associated with poor prognosis of gastric adenocarcinoma. J Cancer Res Clin Oncol. 142:1765–1773. 2016. View Article : Google Scholar : PubMed/NCBI

4 

Yoshino S, Nishikawa K, Morita S, Takahashi T, Sakata K, Nagao J, Nemoto H, Murakami N, Matsuda T, Hasegawa H, et al: Randomised phase III study of S-1 alone versus S-1 plus lentinan for unresectable or recurrent gastric cancer (JFMC36-0701). Eur J Cancer. 65:164–171. 2016. View Article : Google Scholar : PubMed/NCBI

5 

Suzuki M and Nishiahara M: Granulin precursor gene: A sex steroid-inducible gene involved in sexual differentiation of the rat brain. Mol Genet Metab. 75:31–37. 2002. View Article : Google Scholar : PubMed/NCBI

6 

Zhu J, Nathan C, Jin W, Sim D, Ashcroft GS, Wahl SM, Lacomis L, Erdjument-Bromage H, Tempst P, Wright CD and Ding A: Conversion of proepithelin to epithelins: Roles of SLPI and elastase in host defense and wound repair. Cell. 111:867–878. 2002. View Article : Google Scholar : PubMed/NCBI

7 

Tang W, Lu Y, Tian QY, Zhang Y, Guo FJ, Liu GY, Syed NM, Lai Y, Lin EA, Kong L, et al: The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice. Science. 332:478–484. 2011. View Article : Google Scholar : PubMed/NCBI

8 

De Muynck L and Van Damme P: Cellular effects of progranulin in health and disease. J Mol Neurosci. 45:549–560. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Liu CJ and Bosch X: Progranulin: A growth factor, a novel TNFR ligand and a drug target. Pharmacol Ther. 133:124–132. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Swamydas M, Nguyen D, Allen LD, Eddy J and Dréau D: Progranulin stimulated by LPA promotes the migration of aggressive breast cancer cells. Cell Commun Adhes. 18:119–130. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Abrhale T, Brodie A, Sabnis G, Macedo L, Tian C, Yue B and Serrero G: GP88 (PC-Cell derived growth factor, progranulin) stimulates proliferation and confers letrozole resistance to aromatase overexpressing breast cancer cells. BMC Cancer. 11:2312011. View Article : Google Scholar : PubMed/NCBI

12 

Diaz-Cueto L, Arechavaleta-Velasco F, Diaz-Arizaga A, Dominguez-Lopez P and Robles-Flores M: PKC signaling is involved in the regulation of progranulin (acrogranin/PC-cell-derived growth factor/granulin-epithelin precursor) protein expression in human ovarian cancer cell lines. Int J Gynecol Cancer. 22:945–950. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Carlson AM, Maurer MJ, Goergen KM, Kalli KR, Erskine CL, Behrens MD, Knutson KL and Block MS: Utility of progranulin and serum leukocyte protease inhibitor as diagnostic and prognostic biomarkers in ovarian cancer. Cancer Epidemiol Biomarkers Prev. 22:1730–1735. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Cheung PF, Cheng CK, Wong NC, Ho JC, Yip CW, Lui VC, Cheung AN, Fan ST and Cheung ST: Granulin-epithelin precursor is an oncofetal protein defining hepatic cancer stem cells. PLoS One. 6:e282462011. View Article : Google Scholar : PubMed/NCBI

15 

Gao J, Liu D, Li J, Song Q and Wang Q: Effect of STK17A on the sensitivity of ovarian cancer cells to paclitaxel and carboplatin. Oncol Lett. 12:1107–1112. 2016.PubMed/NCBI

16 

Hu Y, Xiao H, Shi T, Oppenheim JJ and Chen X: Progranulin promotes tumour necrosis factor-induced proliferation of suppressive mouse CD4+ Foxp3+ regulatory T cells. Immunology. 142:193–201. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Edelman MJ, Feliciano J, Yue B, Bejarano P, Ioffe O, Reisman D, Hawkins D, Gai Q, Hicks D and Serrero G: GP88 (progranulin): A novel tissue and circulating biomarker for non-small cell lung carcinoma. Hum Pathol. 45:1893–1899. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Dong T, Yang D, Li R, Zhang L, Zhao H, Shen Y, Zhang X, Kong B and Wang L: PGRN promotes migration and invasion of epithelial ovarian cancer cells through an epithelial mesenchymal transition program and the activation of cancer associated fibroblasts. Exp Mol Pathol. 100:17–25. 2016. View Article : Google Scholar : PubMed/NCBI

19 

Wang H, Sun Y, Liu S, Yu H, Li W, Zeng J, Chen C and Jia J: Upregulation of progranulin by helicobacter pylori in human gastric epithelial cells via p38MAPK and MEK1/2 signaling pathway: Role in epithelial cell proliferation and migration. FEMS Immunol Med Microbiol. 63:82–92. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Liu F, Zhang W, Yang F, Feng T, Zhou M, Yu Y, Yu X, Zhao W, Yi F, Tang W and Lu Y: Interleukin-6-stimulated progranulin expression contributes to the malignancy of hepatocellular carcinoma cells by activating mTOR signaling. Sci Rep. 6:212602016. View Article : Google Scholar : PubMed/NCBI

21 

Yang D, Wang LL, Dong TT, Shen YH, Guo XS, Liu CY, Liu J, Zhang P, Li J and Sun YP: Progranulin promotes colorectal cancer proliferation and angiogenesis through TNFR2/Akt and ERK signaling pathways. Am J Cancer Res. 5:3085–3097. 2015.PubMed/NCBI

22 

Tkaczuk KR, Yue B, Zhan M, Tait N, Yarlagadda L, Dai H and Serrero G: Increased circulating level of the survival factor GP88 (progranulin) in the serum of breast cancer patients when compared to healthy subjects. Breast Cancer (Auckl). 5:155–162. 2011.PubMed/NCBI

23 

He Z, Ismail A, Kriazhev L, Sadvakassova G and Bateman A: Progranulin (PC-cell-derived growth factor/acrogranin) regulates invasion and cell survival. Cancer Res. 62:5590–5596. 2002.PubMed/NCBI

24 

Kamrava M, Simpkins F, Alejandro E, Michener C, Meltzer E and Kohn EC: Lysophosphatidic acid and endothelin-induced proliferation of ovarian cancer cell lines is mitigated by neutralization of granulin-epithelin precursor (GEP), a prosurvival factor for ovarian cancer. Oncogene. 24:7084–7093. 2005. View Article : Google Scholar : PubMed/NCBI

25 

Ong CH and Bateman A: Progranulin (granulin-epithelin precursor, PC-cell derived growth factor, acrogranin) in proliferation and tumorigenesis. Histol Histopathol. 18:1275–1288. 2003.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yang D, Li R, Wang H, Wang J, Han L, Pan L, Li X, Kong Q, Wang G, Su X, Su X, et al: Clinical implications of progranulin in gastric cancer and its regulation via a positive feedback loop involving AKT and ERK signaling pathways. Mol Med Rep 16: 9685-9691, 2017.
APA
Yang, D., Li, R., Wang, H., Wang, J., Han, L., Pan, L. ... Su, X. (2017). Clinical implications of progranulin in gastric cancer and its regulation via a positive feedback loop involving AKT and ERK signaling pathways. Molecular Medicine Reports, 16, 9685-9691. https://doi.org/10.3892/mmr.2017.7796
MLA
Yang, D., Li, R., Wang, H., Wang, J., Han, L., Pan, L., Li, X., Kong, Q., Wang, G., Su, X."Clinical implications of progranulin in gastric cancer and its regulation via a positive feedback loop involving AKT and ERK signaling pathways". Molecular Medicine Reports 16.6 (2017): 9685-9691.
Chicago
Yang, D., Li, R., Wang, H., Wang, J., Han, L., Pan, L., Li, X., Kong, Q., Wang, G., Su, X."Clinical implications of progranulin in gastric cancer and its regulation via a positive feedback loop involving AKT and ERK signaling pathways". Molecular Medicine Reports 16, no. 6 (2017): 9685-9691. https://doi.org/10.3892/mmr.2017.7796
Copy and paste a formatted citation
x
Spandidos Publications style
Yang D, Li R, Wang H, Wang J, Han L, Pan L, Li X, Kong Q, Wang G, Su X, Su X, et al: Clinical implications of progranulin in gastric cancer and its regulation via a positive feedback loop involving AKT and ERK signaling pathways. Mol Med Rep 16: 9685-9691, 2017.
APA
Yang, D., Li, R., Wang, H., Wang, J., Han, L., Pan, L. ... Su, X. (2017). Clinical implications of progranulin in gastric cancer and its regulation via a positive feedback loop involving AKT and ERK signaling pathways. Molecular Medicine Reports, 16, 9685-9691. https://doi.org/10.3892/mmr.2017.7796
MLA
Yang, D., Li, R., Wang, H., Wang, J., Han, L., Pan, L., Li, X., Kong, Q., Wang, G., Su, X."Clinical implications of progranulin in gastric cancer and its regulation via a positive feedback loop involving AKT and ERK signaling pathways". Molecular Medicine Reports 16.6 (2017): 9685-9691.
Chicago
Yang, D., Li, R., Wang, H., Wang, J., Han, L., Pan, L., Li, X., Kong, Q., Wang, G., Su, X."Clinical implications of progranulin in gastric cancer and its regulation via a positive feedback loop involving AKT and ERK signaling pathways". Molecular Medicine Reports 16, no. 6 (2017): 9685-9691. https://doi.org/10.3892/mmr.2017.7796
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