ISSN: 1837-9664Journal of Cancer
Global reach, higher impact
J Cancer 2017; 8(10):1818-1825. doi:10.7150/jca.19057 This issue Cite
Research Paper
Hypoxia-inducible factor-1 alpha Correlates with Tumor-Associated Macrophages Infiltration, Influences Survival of Gastric Cancer Patients
1. Department of General surgery, Drum Tower Clinical College of Nanjing Medical University, Nanjing, Jiangsu Province, China;
2. Department of General surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China;
3. Department of Medical, Gastroenterology unit, Nilai Medical Center, Nilai, Negeri Sembilan, Malaysia.
4. Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China;
5. Department of Pathology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China;
6. Department of Radiotherapy, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu Province, China;
7. Department of Pathology, 101th Hospital of PLA, Wuxi, Jiangsu Providence, China;
8. Department of General surgery, 101th Hospital of PLA, Wuxi, Jiangsu Providence, China;
# Wei-jie Zhang, Cheng Chen and Zhi-hua Zhou equally contributed to this study.
Abstract
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-1α), 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-1α 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-1α, infiltration of TAMs and EMT marker in GC tissues. Multivariate Cox analysis revealed that high expression of HIF-1α combined TAMs infiltration were independent prognostic factors for disease-specific survival rate.
Conclusion: HIF-1α 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.
Keywords: Gastric cancer, hypoxia-inducible factor-1 alpha, tumor-associated macrophages, epithelial-mesenchymal transition, prognosis
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