Rabbit Anti-Human Rex1 monoclonal antibody, clone 25I27M0

Purpose: Low-dose CT screening can reduce lung cancer-related mortality. However, CT screening has an FDR of nearly 96%. We sought to assess whether urine samples can be a source for DNA methylation-based detection of non-small cell lung cancer(NSCLC). Experimental Design: This nested case-control study of subjects with suspicious nodules on CT imaging obtained plasma and urine samples preoperatively. Cases (n = 74) had pathologic confirmation of NSCLC. Controls (n = 27) had a noncancer diagnosis. We detected promoter methylation in plasma and urine samples using methylation on beads and quantitative methylation-specific real-time PCR for cancer-specific genes (CDO1, TAC1, HOXA7, HOXA9, SOX17, and ZFP42). Results: DNA methylation at cancer- specific loci was detected in both plasma and urine, and was more frequent in patients with cancer compared with controls for all six genes in plasma and in CDO1, TAC1, HOXA9, and SOX17 in urine. Univariate and multivariate logistic regression analysis showed that methylation detection in each one of six genes in plasma and CDO1, TAC1, HOXA9, and SOX17 in urine were significantly associated with the diagnosis of NSCLC, independent of age, race, and smoking pack-years. When methylation was detected for three or more genes in both plasma and urine, the sensitivity and specificity for lung cancer diagnosis were 73% and 92%, respectively. Conclusions: DNA methylation-based biomarkers in plasma and urine could be useful as an adjunct to CT screening to guide decision-making regarding further invasive procedures in patients with pulmonary nodules.

Objectives: Sasang constitutional medicine is a traditional Korean medicine in which an individual is classified into one of four types of constitution: Taeum (TE), Soeum (SE) Soyang (SY), and Taeyang (TY). These constitution types are determined with biologic and physiologic characteristics, so it has been assumed that genetic factors are associated with each constitution type. Identifying the genetic elements underlying each constitution is necessary for the elucidation of the molecular mechanism of Sasang constitutional medicine. Design: A total of 341,998 genetic loci across the whole genome were genotyped for 1222 subjects of defined constitution type. The genetic loci associated with each constitution type were identified and the functional connectivity of genes within these loci was analyzed using statistical text mining. Results: From the difference in allele frequencies between constitution types, significant genetic loci associated with each type were identified. Chromosomes 3q27.3 (rs10937331, p = 2.71 x 10(-6)), 15q22.2 (rs7180547, p = 1.58 x 10(-6)), and 14q22.3 (rs12431592, p = 1.31 x 10(-6)) were most significantly associated with TE, SE, and SY constitution types, respectively. From the functional relationship analysis using all loci with a p-value <= 10(-4), genes associated with each constitution type were identified. Fifteen (15) genes, including GPM6A, SYT4, and GRIK1, were significantly associated with the TE constitution type (p < 0.05); 12 genes, including DRGX and AKAP11, were significantly associated with the SE constitution type (p < 0.05); and 17 genes, including ZFP42, CDH22, ALDH1A2, OTX2, and EN2, were significantly associated with the SY constitution type (p < 0.05). Conclusions: Genetic loci and genes associated with Sasang constitution types were systematically identified from a genome-wide association study using a large number of subjects.