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Published on: September 3, 2016
NDRG4 in gastric cancer determines tumor cell proliferation and clinical outcome
Zixi Zhang1,2, Junjun She3, Jingyi Yang4
1Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Abstract:
As a novel candidate tumor suppressor, NDRG4 is largely unstudied in human malignancies. In this study, we investigated the protein expression level of NDRG4 in gastric cancer and its association with outcome of patients. In the present study, we recruited 286 patients with gastric cancer and investigated the protein and mRNA expression of NDRG4 in cancer and adjacent normal specimens by immunohistochemistry assay and real-time PCR. The association of NDRG4 level with clinicopathological characteristics was investigated by appropriate statistical analysis. NDRG4 overexpression and knockdown cell lines were established in order to detect its impact on proliferation and apoptosis. Significant decreased protein and mRNA expression of NDRG4 was found in gastric cancer, compared with adjacent normal specimens. Besides, it was found that NDRG4 protein expression in gastric cancer was significantly associated with tumor differentiation, invasion, metastasis, and stage. Patients with tumors of decreased NDRG4 level were more likely to have unfavorable disease-free and overall survival, in both univariate and multivariate analysis. In addition, overexpression of NDRG4 suppressed cell proliferation of gastric cancer cells in vitro; conversely, the proliferation of gastric cancer cells were enhanced by knockdown of NDRG4. These results proved for the first time that NDRG4 could be a potential tumor suppressor and prognostic marker of gastric cancer.
Insights
NDRG4, a novel tumor suppressor, is significantly decreased in gastric cancer. Lower NDRG4 levels correlate with poor patient survival and increased cancer cell proliferation, identifying it as a potential prognostic marker.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- NDRG4 is a novel candidate tumor suppressor with limited study in human cancers.
- Gastric cancer is a significant global health concern with a need for improved prognostic markers.
Purpose of the Study:
- To investigate NDRG4 protein and mRNA expression in gastric cancer.
- To determine the association between NDRG4 levels and patient outcomes.
- To evaluate the role of NDRG4 in gastric cancer cell proliferation and apoptosis.
Main Methods:
- Recruited 286 gastric cancer patients.
- Utilized immunohistochemistry and real-time PCR to assess NDRG4 expression.
- Established NDRG4 overexpression and knockdown cell lines for functional studies.
Main Results:
- NDRG4 protein and mRNA were significantly decreased in gastric cancer tissues compared to normal adjacent tissues.
- Lower NDRG4 expression correlated with poor tumor differentiation, invasion, metastasis, and advanced stage.
- Decreased NDRG4 levels were associated with unfavorable disease-free and overall survival.
- NDRG4 overexpression suppressed gastric cancer cell proliferation, while knockdown enhanced it.
Conclusions:
- NDRG4 acts as a tumor suppressor in gastric cancer.
- NDRG4 is a potential prognostic biomarker for gastric cancer patients.
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