Prognostic Value of Autophagy-related Proteins in Human Gastric Cancer

Abstract

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.

Expression of Four Autophagy-Related Genes Accurately Predicts the Prognosis of Gastrointestinal Cancer in Asian Patients

“…Autophagy influences tumor metastasis, EMT, apoptosis, and drug resistance [ 22 ]. In gastric cancer, the expression pattern of Beclin1, LC3, and P62/SQSTM1, which are autophagy-related genes, predicts the prognosis of the tumor [ 23 – 25 ]. Another study has also identified 4 genes (GRID2, ATG4D, GABARAPL2, and CXCR4) as a potential prognostic marker for predicting the prognosis of GC patients [ 26 ].…”

VE-822 Upregulates the Deubiquitinase OTUD1 to Stabilize FHL1 to Inhibit the Progression of Lung Adenocarcinoma

“…Recently, more targets of VE-822 have been identi ed [33,34]. In this study, screening of CellMiner drug database which include approved drugs in clinical trials revealed that OTUD1 expression was correlated with drug sensitivity of VE-822.…”

Role of autophagy in gastric carcinogenesis

“…First, it can eliminate the injured cellular constituents or whole cells. Second, the energy or nutrients as a result of degradation can provide malignant cells nutrition or be recycled for apoptosis-associated protein synthesis of apoptosis relative proteins[ 55 ]. Specifically, autophagy participates in oncogenesis and tumor progression via two main pillars: a defective pro-death and an excessive pro-survival action.…”

“…Other investigators, by introducing the Kaplan–Meier plotter online database to assess the value of ATG gene expression levels in overall survival prediction in GC patients with different clinical stage, differentiation, gender, HER2 status and therapeutic strategy showed the following: increased levels of ATG3 , ATG4C , ATG5 and ATG10 mRNA were correlated with prolonged overall survival, whereas high levels ATG4B , ATG7 , ATG12 , ATG16L1 and TECPR1 mRNA were correlated with negative overall survival in patients with GC. Therefore, individual ATG estimation by using Kaplan-Meier plotter analysis may offer a guide to clinical therapeutic strategy by means of individualizing gene therapy for GC patients[ 55 ].…”