Cancer Management and Research (Dec 2020)
Prognostic Value of Autophagy-related Proteins in Human Gastric Cancer
Abstract
Minmin Wu,1 Bicheng Chen,1 Xiaodong Pan,2 Jiadong Su3 1Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, People’s Republic of China; 2Department of Transplantation Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, People’s Republic of China; 3Department of Traumatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, People’s Republic of ChinaCorrespondence: Jiadong SuDepartment of Traumatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 Zhejiang Province, People’s Republic of ChinaTel +86 15067839162Email [email protected]: Autophagy-related proteins (ATG) play a crucial role in autophagy. Recently, the functions of autophagy in cancer have been gathering attention. However, the prognostic value of ATGs in gastric cancer (GC) has not been explored.Methods: The Kaplan–Meier plotter (KM plotter) online database was used to examine the value of ATGs gene expression levels in overall survival (OS) prediction in GC patients with different clinical stage, differentiation, gender, HER2 status, and therapeutic strategy. In vitro experiments applied VE-822, an effective GC treatment, to assess cell migration and proliferation in gastric mucosa epithelial cells, and real-time PCR was used to measure alterations of autophagy-related gene expression.Results: High ATG3, ATG4C, ATG5, and ATG10 mRNA levels were associated with good OS, while increased ATG4B, ATG7, ATG12, ATG16L1, and TECPR1 mRNA levels related to unfavorable OS in patients with GC. ATG12 overexpression had different effects on OS due to high levels of heterogeneity. High ATG12 expression was correlated with good OS in female patients with GC and with bad OS for male patients. Additionally, the increased ATG12 expression was more likely to get a satisfactory OS in patients who underwent surgery alone but was associated with poor OS for patients treated with 5-FU adjuvant. In addition, elevated TECPR1 expression was related to favorable OS for patients with poorly differentiated type, while for patients with moderate differentiation, it was relevant to poor OS. The in vitro experiments showed that berzosertib could significantly inhibit the migration and proliferation of human gastric mucosa epithelial cells, and further real-time PCR assessment of ATG expressions partially coincided with the bioinformation analysis above.Conclusion: These results indicate that individual ATGs have unique prognostic significance interpreted using Kaplan–Meier plotter analysis and in vitro experiments, and this may help guide clinical therapeutic strategy and promote OS by individualizing therapy for GC patients.Keywords: autophagy-related proteins, prognostic values, gastric cancer, overall survival
