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We previously developed a novel tumor subtype classification model for duodenal adenocarcinomas based on a combination of the CpG island methylator phenotype (CIMP) and MLH1 methylation status. Here, we tested the prognostic value of this model in stage II colorectal cancer (CRC) patients. Tumors were assigned to CIMP+/MLH1-unmethylated (MLH1-U), CIMP+/MLH1-methylated (MLH1-M), CIMP−/MLH1-U, or CIMP−/MLH1-M groups. Age, tumor location, lymphovascular invasion, and mucin production differed among the four patient subgroups, and CIMP+/MLH1-U tumors were more likely to have lymphovascular invasion and mucin production. Kaplan-Meier analyses revealed differences in both disease-free survival (DFS) and overall survival (OS) among the four groups. In a multivariate analysis, CIMP/MLH1 methylation status was predictive of both DFS and OS, and DFS and OS were shortest in CIMP+/MLH1-U stage II CRC patients. These results suggest that tumor subtype classification based on the combination of CIMP and MLH1 methylation status is informative in stage II CRC patients, and that CIMP+/MLH1-U tumors exhibit aggressive features and are associated with poor clinical outcomes.

BackgroundO6-methylguanine-DNA methyltransferase (MGMT) methylation status has not been extensively investigated in duodenal adenocarcinoma (DA). The aim of this study was to evaluate the MGMT methylation status and examine its possible prognostic value in patients with stage III DA.MethodsDemographics, tumor characteristics and survival were available for 64 patients with stage III DA. MGMT methylation was detected by using MethyLight. A Cox proportional hazard model was built to predict survival, adjusted for clinicopathological characteristics and tumor molecular features, including the CpG island methylator phenotype (CIMP), microsatellite instability (MSI), and KRAS mutations.ResultsMGMT methylation was detected in 17 of 64 (26.6%) patients, and was not correlated with sex, age, tumor differentiation, CIMP, MSI, or KRAS mutations. MGMT methylation was the only one factor associated with both overall survival (OS) and disease-free survival (DFS) on both univariate and multivariate analyses. In patients treated with surgery alone, MGMT-methylated group had worse OS and DFS when compared with MGMT-unmethylated group. However, in patients treated with chemotherapy/radiotherapy, outcomes became comparable between the two groups.ConclusionsOur results demonstrate MGMT methylation is a reliable and independent prognostic factor in DAs. Methylation of MGMT is associated with poor prognosis in patients with stage III DAs.

2020) Physcion 8-O-β-glucopyranoside exerts protective roles in high glucose-induced diabetic retinopathy via regulating lncRNA NORAD/miR-125/ STAT3 signalling, Artificial ABSTRACT Diabetic retinopathy (DR) is the leading cause of decreased vision and blindness globally. The aim of this study was to understand the role of physcion 8-O-b-glucopyranoside (PG) in high glucose (HG)induced DR and to investigate whether lncRNA NORAD/miR-125/STAT3 signalling was the underlying mechanism involved in DR. To this end, the serum levels of NORAD, miR-125, and STAT3 were determined in patients with DR. The APRE-19 cells were subjected to HG treatment to construct the cell model of DR. HG-disposed APRE-19 cell injury was assessed by detecting cell viability, apoptosis, concentrations of pro-inflammatory cytokines including TNF-a and IL-1b, and ROS generation. Moreover, the effect of PG on HG-disposed APRE-19 cell injury was investigated. NORAD was then overexpressed to investigate the combined effects of NORAD overexpression and PG on HG-disposed APRE-19 cell injury. Furthermore, the regulatory relationship between NORAD and miR-125 as well as miR-125 and STAT3 was investigated. The expression levels of NORAD and STAT3 were significantly increased in the serum of DR patients, while the miR-125 expression was decreased. The HG treatment-induced injury to APRE-19 cells, which were alleviated by PG treatment. Moreover, PG alleviated HG-disposed injury to ARPE-19 cells by decreasing NORAD. NORAD negatively regulated miR-125 expression and the combined effects of NORAD and PG on HG-disposed ARPE-19 cell injury were reversed by miR-125 overexpression. Furthermore, STAT3 was confirmed as a target gene of miR-125. Our results show that PG exerts protective roles in HG-disposed DR via regulating lncRNA NORAD/miR-125/STAT3 signalling. NORAD/miR-125/STAT3 axis may provide a novel perspective for target therapy of DR. ARTICLE HISTORY