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Molecular characterizations, including microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP) showed strong associations in colorectal carcinoma (CRC) and provided a deeper understanding of the etiology of disease. However, the global relationship between epigenetic alternations and changes in mRNA expression in CRC remains largely undefined, especially regarding the roles of DNA methyltransferases (DNMTs). Here, we conducted a systematic network comparison to explore the global conservation between co-expressed and co-methylated modules. We successfully identified immune-related modules that were regulated by DNMTs and had strong associations with immune-infiltrating neutrophils and dendritic cells in CRC. Moreover, we found that genes in those modules were prognostic for CRC, with 97.1% (168/ 173) being significantly influenced by DNMTs. Thus, this study resolved an interaction between DNA methylation and mRNA expression through DNMTs. Additionally, we provided evidence that DNMTs control the global hypomethylation of oncogenes, including ALOX5AP and CSF3R that otherwise have high methylation in normal colons. Such genes were also more sensitive to DNMT changes, such as in CRC. Collectively, our analyzes provided a systems biology approach to investigate the association among different molecular phenotypes in diseases.

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BACKGROUND: Plasma level of human ␤-defensin 2 (HBD-2), noted to play a role in lung inflammatory diseases, is elevated in patients with pneumonia. OBJECTIVE: To investigate the prognostic value of plasma HBD-2 concentration in predicting 30-day clinical outcomes in patients with community-acquired pneumonia (CAP). METHODS: Patients with CAP were divided into 2 groups, based on the 30-day clinical outcomes, presence or absence of adverse outcomes (death, need for invasive mechanical ventilation, development of new complication of pneumonia). Demographic data, comorbidities, baseline clinical and laboratory features, plasma HBD-2 concentration, and the CURB-65 (confusion, urea nitrogen, breathing frequency, blood pressure, > 65 years of age) scores on admission were compared between the 2 groups in univariable analysis. Multivariable logistic regression was used to test the predictor of adverse outcomes. Receiver operating characteristic analyses were used to calculate the power of the assays to predict the 30-day adverse outcomes. RESULTS: We enrolled 361 subjects with CAP between March 2007 and March 2011. Univariate analysis revealed the following as predictive factors: age, smoking status, duration from symptom onset to admission, bilateral radiographic changes, total white-blood-cell count, serum sodium, serum potassium, serum albumin, plasma HBD-2 concentration, CURB-65 score, and comorbidities. In the multivariable logistic regression, plasma HBD-2 concentration, CURB-65 score, and age were independent predictors of 30-day adverse outcomes. In the receiver operating characteristic analysis, plasma HBD-2 concentration had an area under the curve of 0.77 (95% CI 0.71-0.82); the optimal cutoff point was 12.5 mg/L (sensitivity of 63%, specificity of 84%, positive predictive value of 42%, and negative predictive value of 88%), which predicted 30-day adverse outcomes in subjects with CAP. CONCLUSIONS: In CAP patients, plasma HBD-2 level on admission is associated with 30-day clinical outcomes, and lower plasma HBD-2 level is an independent predictor for adverse outcomes. Plasma HBD-2 level may become a useful tool for prognostic stratification in patients with CAP.