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
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  • Published online on: October 17, 2017     https://doi.org/10.3892/mmr.2017.7796
  • Pages: 9685-9691
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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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December-2017
Volume 16 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

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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