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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.

SUBMITTER: Zhao Y

PROVIDER: S-EPMC3629069 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Abnormal methylation of seven genes and their associations with clinical characteristics in early stage non-small cell lung cancer.

Zhao Yangxing Y Zhou Huafu H Ma Kelong K Sun Jinfeng J Feng Xu X Geng Junfeng J Gu Jun J Wang Wei W Zhang Hongyu H He Yinghua Y Guo Shicheng S Zhou Xiaoyu X Yu Jian J Lin Qiang Q

Oncology letters 20130129 4

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 FOLX ...[more]

PMID: 23599765

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Project description:The diagnosis of small cell lung carcinoma (SCLC) remains a great challenge. Changes in chromosome 3p (chr3) genes are usually observed in the pathogenesis of lung cancer, which suggests that these chr3 genes may be a diagnostic marker in the early stage of SCLC. The present study explored the diagnostic value of the chr3 gene in SCLC using Bioinformatics. Furthermore, reverse transcription-quantitative PCR (RT-qPCR) was used to reveal the expression patterns of diagnostic biomarkers in human pulmonary alveolar epithelial cells and in the SCLC cell line NCI-H146. A total of 33 differentially expressed (DE) chr3 genes and 1,156 module genes associated with clinical features of patients with SCLC were identified and functional enrichment analysis indicated that all these genes were significantly enriched in cell cycle terms. The area under the receiver operating characteristic curve demonstrated that the overlapping genes of the DE-chr3 and module genes, namely cell division cycle 25 A (CDC25A), FYVE and coiled-coil domain autophagy adaptor 1 (FYCO1) and lipid raft linker 1 (RFTN1), were relatively accurate in distinguishing normal from SCLC samples, and may thus be considered diagnostic biomarkers. CDC25A was overexpressed in SCLC samples, while FYCO1 and RFTN1 were highly expressed in normal samples, as evidenced by the RT-qPCR results. Single-gene gene set enrichment analysis suggested that the diagnostic biomarkers were significantly associated with cell cycle, ATP-binding cassette transporter, immune cell differentiation, immune response and multiple respiratory disease pathways. Furthermore, a total of 141 drugs were predicted by The Comparative Toxicogenomics Database to be able to modulate the expression of the diagnostic biomarkers, of which 8 drugs were shared among the three aforementioned diagnostic biomarkers. The present study identified three novel and powerful diagnostic biomarkers for SCLC based on chr3 genes. Suggestions for the development and selection of drugs for clinical treatment based on diagnostic biomarkers were also provided.

Dataset Information

Abnormal methylation of seven genes and their associations with clinical characteristics in early stage non-small cell lung cancer.

Publications

Abnormal methylation of seven genes and their associations with clinical characteristics in early stage non-small cell lung cancer.

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