ABSTRACT
Identifying sensitive and specific biomarkers for early detection of cancer is immensely imperative for early diagnosis and treatment and better clinical outcome of cancer patients. This study aimed to construct a specific DNA methylation pattern of cancer suppressor genes and explore the feasibility of applying cell-free DNA based methylation as a biomarker for early diagnosis of esophageal squamous cell carcinoma (ESCC). We recruited early stage ESCC patients from Yangzhong County, China. The Illumina Infinium 450K Methylation BeadChip was used to construct a genome-wide DNA methylation profile. Then, differentiated genes were selected for the validation study using the Sequenom MassARRAY platform. The frequency of methylation was compared between cancer tissues, matched cell-free DNAs and normal controls. The specific methylation profiles were constructed, and the sensitivity and specificity were calculated. Seven CG sites in three genes CASZ1, CDH13 and ING2 were significantly hypermethylated in ESCC as compared with normal controls. A significant correlation was found between the methylation of DNA extracted from cancer tissues and matched plasma cell-free DNA, either for individual CG site or for cumulative methylation analysis. The sensitivity and specificity reached 100% at an appropriate cut-point using these specific methylation biomarkers. This study revealed that aberrant DNA methylation is a promising biomarker for molecular diagnosis of esophageal cancer. Hypermethylation of CASZ1, CDH13 and ING2 detected in plasma cell-free DNA can be applied as a potential noninvasive biomarker for diagnosis of esophageal cancer.
ABSTRACT
OBJECTIVE: Blood pressure (BP) load, defined as the percentage of abnormally elevated BP readings, is usually provided on the report of ambulatory BP monitoring. However, the usefulness of BP load is still uncertain. In the present study, we examined whether BP load would be associated, independently of BP level, with target organ damage. METHODS: We recruited 869 individuals (430 men, mean age 51 years) who were referred for 24-h ambulatory BP monitoring and were off antihypertensive medication for at least 2 weeks. BP load was defined as the percentage of daytime and nighttime SBP/DBP readings at least 135/85 and at least 120/70 mmHg, respectively. Brachial-ankle pulse wave velocity (baPWV) and carotid-femoral pulse wave velocity (cfPWV), left ventricular mass index (LVMI) and urinary albumin-to-creatinine ratio (ACR) were determined as measures of target organ damage. RESULTS: SBP and DBP load had a skewed distribution (P<0.001). In multivariate-adjusted categorical analyses, baPWV (13.8, 14.6 and 15.6 m/s), cfPWV (7.4, 7.7 and 8.4 m/s), LVMI (90.1, 94.8 and 100.7 g/m) and ACR (0.47, 0.58 and 0.77 mg/mmol) all increased from tertiles 1-3 of SBP load (P<0.001). However, these differences became nonsignificant (P ≥ 0.16) after additionally adjusted for 24-h SBP level. In a continuous analysis in individuals with a BP load greater than zero (n=838), adding the logarithmically transformed SBP load did not improve the fit of models relating measures of target organ damage to SBP level (P ≥ 0.14), except for cfPWV (P=0.01) that was however negatively associated with BP load. Analyses on DBP load produced similar results. CONCLUSION: BP load was associated with target organ damage, but not independently of BP level.
