title: Abnormal methylation of seven genes and their associations with clinical characteristics in early stage non-small cell lung cancer.
abstract: To identify novel abnormally methylated genes in early stage non-small cell lung cancer (NSCLC), we analyzed the methylation status of 13 genes (ALX1, BCL2, FOXL2, HPP1, MYF6, OC2, PDGFRA, PHOX2A, PITX2, RARB, SIX6, SMPD3 and SOX1) in cancer tissues from 101 cases of stage I NSCLC patients and lung tissues from 30 cases of non-cancerous lung disease controls, using methylation-specific PCR (MSP). The methylation frequencies (29.70-64.36%) of 7 genes (MYF6, SIX6, SOX1, RARB, BCL2, PHOX2A and FOLX2) in stage I NSCLC were significantly higher compared with those in non-cancerous lung disease controls (P<0.05). The co-methylation of SIX6 and SOX1, or the co-methyaltion of SIX6, RARB and SOX1 was associated with adenosquamous carcinoma (ADC), and the co-methylation of BCL2, RARB and SIX6 was associated with smoking. A panel of 4 genes (MYF6, SIX6, BCL2 and RARB) may offer a sensitivity of 93.07% and a specificity of 83.33% in the diagnosis of stage I NSCLC. Furthermore, we also detected the expression of 8 pathological markers (VEGF, HER-2, P53, P21, EGFR, CHGA, SYN and EMA) in cancer tissues of stage I NSCLC by immunohistochemistry, and found that high expression levels of p53 and CHGA were associated with the methylation of BCL2 (P=0.025) and PHOX2A (P=0.023), respectively. In this study, among the 7 genes which demonstrated hypermethylation in stage I NSCLC compared with non-cancerous lung diseases, 5 genes (MYF6, SIX6, PHOX2A, FOLX2 and SOX1) were found for the first time to be abonormally methylated in NSCLC. Further study of these genes shed light on the carcinogenesis of NSCLC.
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032;
authors.forename: Yangxing
authors.initials: Y
authors.lastname: Zhao
authors.forename: Huafu
authors.initials: H
authors.lastname: Zhou
authors.forename: Kelong
authors.initials: K
authors.lastname: Ma
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Sun
authors.forename: Xu
authors.initials: X
authors.lastname: Feng
authors.forename: Junfeng
authors.initials: J
authors.lastname: Geng
authors.forename: Jun
authors.initials: J
authors.lastname: Gu
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhang
authors.forename: Yinghua
authors.initials: Y
authors.lastname: He
authors.forename: Shicheng
authors.initials: S
authors.lastname: Guo
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Zhou
authors.forename: Jian
authors.initials: J
authors.lastname: Yu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Lin
keywords: DNA methylation; non-small cell lung cancer; smoking; stage I