A low DNA methylation epigenotype in lung squamous cell carcinoma and its association with idiopathic pulmonary fibrosis and poorer prognosis
| العنوان: | A low DNA methylation epigenotype in lung squamous cell carcinoma and its association with idiopathic pulmonary fibrosis and poorer prognosis |
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| المؤلفون: | Takahiro Nakajima, Masaki Fukuyo, Satoshi Ota, Hidemi Suzuki, Atsushi Hata, Junichi Morimoto, Keisuke Matsusaka, Ichiro Yoshino, Atsushi Kaneda, Hironobu Wada, Yuichi Sakairi, Bahityar Rahmutulla, Takayoshi Yamamoto, Hisahiro Matsubara |
| المصدر: | International Journal of Cancer. 146:388-399 |
| بيانات النشر: | Wiley, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, Oncology, Cancer Research, medicine.medical_specialty, Lung Neoplasms, Multivariate analysis, Kaplan-Meier Estimate, Epigenesis, Genetic, 03 medical and health sciences, Idiopathic pulmonary fibrosis, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Internal medicine, Biomarkers, Tumor, medicine, Humans, Lung cancer, Lung, Gene, Aged, business.industry, Lung squamous cell carcinoma, DNA Methylation, Middle Aged, respiratory system, Prognosis, medicine.disease, Idiopathic Pulmonary Fibrosis, respiratory tract diseases, stomatognathic diseases, medicine.anatomical_structure, 030220 oncology & carcinogenesis, DNA methylation, Carcinoma, Squamous Cell, Pyrosequencing, Female, business |
| الوصف: | Patients with idiopathic pulmonary fibrosis (IPF) have higher risk of developing lung cancer, for example, squamous cell carcinoma (SCC), and show poor prognosis, while the molecular basis has not been fully investigated. Here we conducted DNA methylome analysis of lung SCC using 20 SCC samples with/without IPF, and noncancerous lung tissue samples from smokers/nonsmokers, using Infinium HumanMethylation 450K array. SCC was clustered into low- and high-methylation epigenotypes by hierarchical clustering analysis. Genes hypermethylated in SCC significantly included genes targeted by polycomb repressive complex in embryonic stem cells, and genes associated with Gene Ontology terms, for example, "transcription" and "cell adhesion," while genes hypermethylated specifically in high-methylation subgroup significantly included genes associated with "negative regulation of growth." Low-methylation subgroup significantly correlated with IPF (78%, vs. 17% in high-methylation subgroup, p = 0.04), and the correlation was validated by additional Infinium analysis of SCC samples (n = 44 in total), and data from The Cancer Genome Atlas (n = 390). The correlation between low-methylation subgroup and IPF was further validated by quantitative methylation analysis of marker genes commonly hypermethylated in SCC (HOXA2, HOXA9 and PCDHGB6), and markers specifically hypermethylated in high-methylation subgroup (DLEC1, CFTR, MT1M, CRIP3 and ALDH7A1) in 77 SCC cases using pyrosequencing (p = 0.003). Furthermore, low-methylation epigenotype significantly correlated with poorer prognosis among all SCC patients, or among patients without IPF. Multivariate analysis showed that low-methylation epigenotype is an independent predictor of poor prognosis. These may suggest that lung SCC could be stratified into molecular subtypes with distinct prognosis, and low-methylation lung SCC that significantly correlates with IPF shows unfavorable outcome. |
| تدمد: | 1097-0215 0020-7136 |
| DOI: | 10.1002/ijc.32532 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ea3e68a61646d8eac82933647fa40874 https://doi.org/10.1002/ijc.32532 |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....ea3e68a61646d8eac82933647fa40874 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10970215 00207136 |
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| DOI: | 10.1002/ijc.32532 |