Prediction of Efficacy of Postoperative Chemotherapy by DNA Methylation of CDO1 in Gastric Cancer

2020 ◽  
Vol 256 ◽  
pp. 404-412
Author(s):  
Hiroki Harada ◽  
Takafumi Soeno ◽  
Keigo Yokoi ◽  
Nobuyuki Nishizawa ◽  
Hideki Ushiku ◽  
...  
2019 ◽  
Author(s):  
Yi Bai ◽  
Chunlian Wei ◽  
Yuxin Zhong ◽  
Junyu Long ◽  
Shan Huang ◽  
...  

2019 ◽  
Vol 19 (10) ◽  
pp. 817-827
Author(s):  
Jianbo Zhu ◽  
Lijuan Deng ◽  
Baozhen Chen ◽  
Wenqing Huang ◽  
Xiandong Lin ◽  
...  

Background:Recurrence is the leading cause of treatment failure and death in patients with gastric cancer (GC). However, the mechanism underlying GC recurrence remains unclear, and prognostic markers are still lacking.Methods:We analyzed DNA methylation profiles in gastric cancer cases with shorter survival (<1 year) or longer survival (> 3 years), and identified candidate genes associated with GC recurrence. Then, the biological effects of these genes on gastric cancer were studied.Results:A novel gene, magnesium-dependent phosphatase 1 (mdp1), was identified as a candidate gene whose DNA methylation was higher in GC samples from patients with shorter survival and lower in patients with longer survival. MDP1 protein was highly expressed in GC tissues with longer survival time, and also had a tendency to be expressed in highly differentiated GC samples. Forced expression of MDP1 in GC cell line BGC-823 inhibited cell proliferation, whereas the knockdown of MDP1 protein promoted cell growth. Overexpression of MDP1 in BGC-823 cells also enhanced cell senescence and apoptosis. Cytoplasmic kinase protein c-Jun N-terminal kinase (JNK) and signal transducer and activator of transcription 3 (Stat3) were found to mediate the biological function of MDP1.Conclusion:These results suggest that MDP1 protein suppresses the survival of gastric cancer cells and loss of MDP expression may benefit the recurrence of gastric cancer.


Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 854
Author(s):  
Yishu Wang ◽  
Lingyun Xu ◽  
Dongmei Ai

DNA methylation is an important regulator of gene expression that can influence tumor heterogeneity and shows weak and varying expression levels among different genes. Gastric cancer (GC) is a highly heterogeneous cancer of the digestive system with a high mortality rate worldwide. The heterogeneous subtypes of GC lead to different prognoses. In this study, we explored the relationships between DNA methylation and gene expression levels by introducing a sparse low-rank regression model based on a GC dataset with 375 tumor samples and 32 normal samples from The Cancer Genome Atlas database. Differences in the DNA methylation levels and sites were found to be associated with differences in the expressed genes related to GC development. Overall, 29 methylation-driven genes were found to be related to the GC subtypes, and in the prognostic model, we explored five prognoses related to the methylation sites. Finally, based on a low-rank matrix, seven subgroups were identified with different methylation statuses. These specific classifications based on DNA methylation levels may help to account for heterogeneity and aid in personalized treatments.


Epigenetics ◽  
2021 ◽  
pp. 1-7
Author(s):  
Fernanda Wisnieski ◽  
Jaqueline Cruz Geraldis ◽  
Leonardo Caires Santos ◽  
Mariana Ferreira Leal ◽  
Danielle Queiroz Calcagno ◽  
...  

2010 ◽  
Vol 28 (35) ◽  
pp. 5210-5218 ◽  
Author(s):  
Christoph Schuhmacher ◽  
Stephan Gretschel ◽  
Florian Lordick ◽  
Peter Reichardt ◽  
Werner Hohenberger ◽  
...  

PurposePatients with locally advanced gastric cancer benefit from combined pre- and postoperative chemotherapy, although fewer than 50% could receive postoperative chemotherapy. We examined the value of purely preoperative chemotherapy in a phase III trial with strict preoperative staging and surgical resection guidelines.Patients and MethodsPatients with locally advanced adenocarcinoma of the stomach or esophagogastric junction (AEG II and III) were randomly assigned to preoperative chemotherapy followed by surgery or to surgery alone. To detect with 80% power an improvement in median survival from 17 months with surgery alone to 24 months with neoadjuvant, 282 events were required.ResultsThis trial was stopped for poor accrual after 144 patients were randomly assigned (72:72); 52.8% patients had tumors located in the proximal third of the stomach, including AEG type II and III. The International Union Against Cancer R0 resection rate was 81.9% after neoadjuvant chemotherapy as compared with 66.7% with surgery alone (P = .036). The surgery-only group had more lymph node metastases than the neoadjuvant group (76.5% v 61.4%; P = .018). Postoperative complications were more frequent in the neoadjuvant arm (27.1% v 16.2%; P = .09). After a median follow-up of 4.4 years and 67 deaths, a survival benefit could not be shown (hazard ratio, 0.84; 95% CI, 0.52 to 1.35; P = .466).ConclusionThis trial showed a significantly increased R0 resection rate but failed to demonstrate a survival benefit. Possible explanations are low statistical power, a high rate of proximal gastric cancer including AEG and/or a better outcome than expected after radical surgery alone due to the high quality of surgery with resections of regional lymph nodes outside the perigastic area (celiac trunc, hepatic ligament, lymph node at a. lienalis; D2).


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