High expression of death-associated protein 5 promotes glucose metabolism in gastric cancer cells and correlates with poor survival outcomes.
10.12122/j.issn.1673-4254.2023.07.02
- Author:
Qiusheng WANG
1
;
Zhen ZHANG
1
;
Lian WANG
1
;
Yu WANG
2
;
Xinyu YAO
2
;
Yueyue WANG
3
;
Xiaofeng ZHANG
4
;
Sitang GE
1
;
Lugen ZUO
1
Author Information
1. Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China.
2. Bengbu Medical College, Bengbu 233030, China.
3. Department of Gastrointestinal Surgery, Clinical Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China.
4. Central Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China.
- Publication Type:Journal Article
- Keywords:
aerobic glycolysis;
bioinformatics;
death-associated protein 5;
gastric cancer;
prognosis
- MeSH:
Humans;
Stomach Neoplasms;
Blotting, Western;
Databases, Factual;
Glucose;
Lactates
- From:
Journal of Southern Medical University
2023;43(7):1063-1070
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the prognostic value of death-associated protein 5 (DAP5) in gastric cancer (GC) and its regulatory effect on aerobic glycolysis in GC cells.
METHODS:We analyzed DAP5 expression levels in GC and adjacent tissues and its association with survival outcomes of GC patients using public databases. We collected paired samples of GC and adjacent tissues from 102 patients undergoing radical resection of GC in our hospital from June, 2012 to July, 2017, and analyzed the correlation of DAP5 expression level detected immunohistochemically with the clinicopathological parameters of the patients. Cox regression analysis, Kaplan-Meier analysis, and ROC curves were used to explore the independent risk factors and the predictive value of DAP5 expression for 5-year survival of the patients. In the cell experiments, we observed the changes in aerobic glycolysis in MGC-803 cells following lentivirus-mediated DAP5 knockdown or overexpression by measuring glucose uptake and cellular lactate level and using qRT-PCR and Western blotting.
RESULTS:Analysis using the public databases showed that DAP5 was highly expressed in GC and correlated with tumor progression and poor survival outcomes of the patients (P < 0.05). In the clinical samples, DAP5 expression was significantly higher in GC than in the adjacent tissues (3.19±0.60 vs 1.00±0.12; t=36.863, P < 0.01), and a high expression of DAP5 was associated with a reduced 5-year survival rate of the patients (17.6% vs 72.5%; χ2=29.921, P < 0.05). A high DAP5 expression, T3-4, N2-3, and CEA≥5 ng/mL were identified as independent risk factors affecting 5-year survival outcomes of GC (P < 0.05), for which DAP5 expression showed a prediction sensitivity, specificity and accuracy of 73.2%, 80.4% and 79.0%, respectively. In MGC-803 cells, DAP5 knockdown significantly reduced glucose uptake, lactate level and the expressions of GLUT1, HK2 and LDHA, and DAP5 overexpression produced the opposite effects (P < 0.05).
CONCLUSION:A high expression of DAP5 in GC, which enhances cellular aerobic glycolysis to promote cancer progression, is correlated with a poor survival outcome and may serve as a biomarker for evaluating long-term prognosis of GC patients.
