期刊
JOURNAL OF CANCER
卷 8, 期 10, 页码 1818-1825出版社
IVYSPRING INT PUBL
DOI: 10.7150/jca.19057
关键词
Gastric cancer; hypoxia-inducible factor-1 alpha; tumor-associated macrophages; epithelial-mesenchymal transition; prognosis
类别
资金
- National Natural Science Foundation of China [81201909, 81572338, 81672380]
- Fundamental Research Funds for the Central Universities [021414380031]
- Nanjing Medical Science and Technology Development program [YKK12072, YKK15061, YKK16078]
- Jiangsu provincial Six Talent Peaks [WSN-078]
Background: Hypoxia was a common feature for accelerating tumor metastasis by both inducting epithelial-mesenchymal transition (EMT) of tumor cells and polarization of tumor-associated macrophages (TAMs). The association and roles between hypoxia, EMT and TAMs in the biological behavior of gastric cancer (GC) for the time being recurrence is unclear. Material and methods: hypoixa by expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha), polarized functional status of infiltrated TAMs by immunohistochemical staining of CD68 and CD163, and the expression of E-cadherin as EMT property had been evaluated in 236 patients consecutive with histologically confirmed GC. Clinical significance was assessed for all these patients. Results: High expression of HIF-1 alpha was found in patients with aggressive features, especially for recurrent patients. High infiltration of TAMs and abnormal expression of EMT-marker were also related to aggressive characteristics and predicted poor prognosis in GC. Meanwwhile, there existed a significant correlation among expression of HIF-1 alpha, infiltration of TAMs and EMT marker in GC tissues. Multivariate Cox analysis revealed that high expression of HIF-1 alpha combined TAMs infiltration were independent prognostic factors for disease-specific survival rate. Conclusion: HIF-1 alpha is an unfavorable indicator for prognosis, may promote tumor progression through the induction of EMT and establishment of a pro-tumor immunosuppressive microenvironment. Further investigation into the therapeutic effects of blocking hypoxia is possible a potential strategy for GC treatment.
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