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DNA methylation is a critical epigenetic mechanism involved in key cellular processes. Its deregulation has been linked to many human cancers including esophageal squamous cell carcinoma (ESCC). This study was designed to explore the whole methylation status of ESCC and to identify potential plasma biomarkers for early diagnosis. We used Infinium Methylation 450k array to analyze ESCC tissues (n = 4), paired normal surrounding tissues (n = 4) and normal mucosa from healthy individuals (n = 4), and combined these with gene expression data from the GEO database. One hundred and sixty eight genes had differentially methylated CpG sites in their promoter region and a gene expression pattern inverse to the direction of change in DNA methylation. These genes were involved in several cancer-related pathways. Three genes were validated in additional 42 ESCC tissues and paired normal surrounding tissues. The methylation frequency of EPB41L3, GPX3, and COL14A1 were higher in tumor tissues than in normal surrounding tissues (P<0.017). The higher methylation frequency of EPB41l3 was correlated with large tumor size (P = 0.044) and advanced pT tumor stage (P = 0.001). The higher methylation frequency of GPX3 and COL14A1 were correlated with advanced pN tumor stage (P = 0.001 and P<0.001). The methylation of EPB41L3, GPX3, and COL14A1 genes were only found in ESCC patients' plasma, but not in normal individuals upon testing 42 ESCC patients and 50 healthy individuals. Diagnostic sensitivity was increased when methylation of any of the 3 genes were counted (64.3% sensitivity and 100% specificity). These differentially methylated genes in plasma may be used as biomarkers for early diagnosis of ESCC.

ObjectiveTo explore the association between glycated hemoglobin (A1C) variability and renal disease progression in patients with diabetes mellitus.MethodsA comprehensive search was performed using the PubMed and Embase databases (up to April 26, 2014). The hazard ratio (HR) was pooled per unit increase in the standard deviation of A1C (A1C-SD) to evaluate the dose-response relationship between A1C-SD and the risk of nephropathy.ResultsEight studies with a total of 17,758 subjects provided the HR for A1C-SD and were included in the final meta-analysis. The pooled HR results demonstrated that A1C-SD was significantly associated with the progression of renal status (HR for both T1DM and T2DM 1.43, 95% confidence interval [CI] 1.24–1.64; HR for T1DM 1.70, 95%CI 1.41–2.05; HR for T2DM 1.20, 95%CI 1.12–1.28). A1C-SD was significantly correlated with new-onset microalbuminuria (HR for T1DM 1.63, 95%CI 1.28–2.07; HR for T2DM 1.23, 95%CI 1.08–1.39). These outcomes were also supported in subgroup analyses. Furthermore, sensitivity analyses demonstrated that the results were robust.ConclusionsA1C variability is independently associated with the development of microalbuminuria and the progression of renal status in both type 1 and 2 diabetes patients. A standard method for measuring A1C variability is essential for further and deeper analyses. In addition, future studies should assess the effect of reducing A1C variability on nephropathy complication.

Difference in HPV 16/18 infection in lung cancer patients from Wuhan, China and Taichung, Taiwan suggests that HPV 16/18 might play a different role in lung cancer development among Chinese living in different areas.