NDRG4 in gastric cancer determines tumor cell proliferation and clinical outcome

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.

Network Structure Analysis Identifying Key Genes of Autism and Its Mechanism

“…Consistent with these findings, the expression of neuroprotective factor BDNF in NDRG4−/− mice decreased [34]. Reference [35] demonstrated for the first time that NDRG4 may be a potential tumor suppressor gene and prognostic marker for gastric cancer. Chen et al [36] explained the risk of gastric cancer caused by hypermethylation of NDRG4 promoter.…”

N-MYC Downstream Regulated Gene 4 (NDRG4), a Frequent Downregulated Gene through DNA Hypermethylation, plays a Tumor Suppressive Role in Esophageal Adenocarcinoma

“…In fact, NDRG4 is upregulated in tumors of central nerve system, such as glioblastoma [28] and meningioma [40], functioning as an oncogene. However, in gastrointestinal tract tumors, current evidences demonstrated that NDRG4 is downregulated in gastric cancers [26,29] and colorectal cancers [27,41], suggesting that it may function as a tumor suppressor. Our data, showing its downregulation in EAC, support the evidence that NDRG4 behaves differently in gastrointestinal tumors.…”

“…NDRG4 is the last identified human NDRG member. The role of NDRG4 in human tumorigenesis is barely known and quite controversial [26][27][28][29][30]. Most of the recent studies reported an elevation of NDRG4 in brain tumors [28], where it promoted cell cycle progression and survival of glioblastoma cells.…”

“…Most of the recent studies reported an elevation of NDRG4 in brain tumors [28], where it promoted cell cycle progression and survival of glioblastoma cells. On the other hand, NDRG4 was downregulated in gastrointestinal tract cancers and acted as a potential tumor suppressor [27,29]. DNA hypermethylation of NDRG4 was frequently detected in colorectal cancers [27].…”

Hypermethylation-mediated silencing of NDRG4 promotes pancreatic ductal adenocarcinoma by regulating mitochondrial function

“…This inverse effect may indicate that NDRG4 expression has tissue-specific function in different types of cancer. In gastric cancer, significantly decreased expression levels of NDRG4 protein and mRNA are more likely to lead to poor prognosis (14). In colon and breast cancers, NDRG4 expression is decreased during the carcinogenesis process.…”