Epigenetic clustering of lung adenocarcinomas based on DNA methylation profiles in adjacent lung tissue: Its correlation with smoking history and chronic obstructive pulmonary disease

摘要: The aim of this study was to clarify the significance DNA methylation alterations during lung carcinogenesis. Infinium assay performed using 139 paired samples non-cancerous tissue (N) and tumorous (T) from a learning cohort patients with adenocarcinomas (LADCs). Fifty N T validation were also analyzed. on 1,928 probes occurred in relative normal without primary tumors, inherited by, or strengthened in, samples. Unsupervised hierarchical clustering levels all 26,447 subclustered into Cluster I (n = 32), II 35) III 72). LADCs developed inflammatory background chronic obstructive pulmonary disease (COPD) heavy smokers locally invasive. Most non-smokers had favorable outcome. light most aggressive (frequently showing lymphatic blood vessel invasion, lymph node metastasis an advanced pathological stage), poor hallmark genes for each cluster, such as IRX2, HOXD8, SPARCL1, RGS5 EI24, again correlated clinicopathological characteristics cohort. profiles reflecting carcinogenetic factors smoking COPD appear be established may determine aggressiveness tumors developing individual patients, thus patient