Journal
CANCER BIOMARKERS
Volume 34, Issue 1, Pages 55-66Publisher
IOS PRESS
DOI: 10.3233/CBM-210334
Keywords
ECRG4; gastric cancer; immunohistochemistry; prognosis; data mining
Categories
Funding
- Foundation of Ningxia Medical University [XZ2019011]
- National Natural Science Foundation of China [81860426]
- Natural Science Foundation of Ningxia, China [2021AAC03318]
- Construction Project of Healthy Ningxia [2021-NW-091]
- Key Research and Development Program of Ningxia, China [2019BEG03005]
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This study reveals that ECRG4 expression is significantly downregulated in gastric cancer, and low ECRG4 expression is associated with higher histological grade, lymph node metastasis, invasive depth, advanced tumor stage, and poor overall survival. In addition, silencing of ECRG4 expression promotes gastric cancer cell growth and invasion. The findings suggest that ECRG4 plays an important role in the pathogenesis and progression of gastric cancer and may serve as a prognostic biomarker for this disease.
BACKGROUND: We have previously characterized esophageal carcinoma-related gene 4 (ECRG4) as a novel tumor suppressor gene, which is frequently inactivated in nasopharyngeal carcinoma and breast cancer. Nevertheless, the expression status and prognostic significance of ECRG4 maintain elusive in human gastric cancer. Herein, we examined ECRG4 expression profile in gastric cancer and assessed its association with clinicopathological characteristics and patient survival. METHODS: Online data mining, real-time RT-PCR and immunohistochemistry were employed to determined ECRG4 expression at transcriptional and protein levels in tumors vs. noncancerous tissues. Statistical analyses including the Kaplan-Meier survival analysis and the Cox hazard model were utilized to detect the impact on clinical outcome. Moreover, ECRG4 expression was silenced in gastric cancer SGC7901 cells, and cell proliferation, colony formation and invasion assays were carried out. RESULTS: ECRG4 mRNA and protein levels were obviously downregulated in cancer tissues than noncancerous tissues. Statistical analyses demonstrated that low ECRG4 expression was found in 34.5% (58/168) of primary gastric cancer tissues, which was associated with higher histological grade (P = 0.018), lymph node metastasis (P = 0.011), invasive depth (P = 0.020), advanced tumor stage (P = 0.002) and poor overall survival (P < 0.001). Multivariate analysis showed ECRG4 expression is an independent prognostic predictor (P < 0.001). Silencing ECRG4 expression promoted gastric cancer cell growth and invasion. Western blot analysis revealed the anti-metastatic functions of ECRG4 by downregulating of E-cadherin and cx-Catenin, as well as upregulating N-cadherin and Vimentin. CONCLUSIONS: Our observations reveal that ECRG4 expression is involved in gastric cancer pathogenesis and progression, and may serve as a candidate prognostic biomarker for this disease.
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