Genome-wide DNA methylation profiling reveals novel epigenetic signatures in squamous cell lung cancer
Abstract Background Epigenetic alterations are strongly associated with the development of cancer. The aim of this study was to identify epigenetic pattern in squamous cell lung cancer (LUSC) on a genome-wide scale. Results Here we performed DNA methylation profiling on 24 LUSC and paired non-tumor...
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BMC
2017-11-01
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| Series: | BMC Genomics |
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| Online Access: | http://link.springer.com/article/10.1186/s12864-017-4223-3 |
| _version_ | 1818518846436278272 |
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| author | Yuan-Xiang Shi Ying Wang Xi Li Wei Zhang Hong-Hao Zhou Ji-Ye Yin Zhao-Qian Liu |
| author_facet | Yuan-Xiang Shi Ying Wang Xi Li Wei Zhang Hong-Hao Zhou Ji-Ye Yin Zhao-Qian Liu |
| author_sort | Yuan-Xiang Shi |
| collection | DOAJ |
| description | Abstract Background Epigenetic alterations are strongly associated with the development of cancer. The aim of this study was to identify epigenetic pattern in squamous cell lung cancer (LUSC) on a genome-wide scale. Results Here we performed DNA methylation profiling on 24 LUSC and paired non-tumor lung (NTL) tissues by Illumina Human Methylation 450 K BeadArrays, and identified 5214 differentially methylated probes. By integrating DNA methylation and mRNA expression data, 449 aberrantly methylated genes accompanied with altered expression were identified. Ingenuity Pathway analysis highlighted these genes which were closely related to the carcinogenesis of LUSC, such as ERK family, NFKB signaling pathway, Hedgehog signaling pathway, providing new clues for understanding the molecular mechanisms of LUSC pathogenesis. To verify the results of high-throughput screening, we used 56 paired independent tissues for clinical validation by pyrosequencing. Subsequently, another 343 tumor tissues from the Cancer Genome Atlas (TCGA) database were utilized for further validation. Then, we identified a panel of DNA methylation biomarkers (CLDN1, TP63, TBX5, TCF21, ADHFE1 and HNF1B) in LUSC. Furthermore, we performed receiver operating characteristics (ROC) analysis to assess the performance of biomarkers individually, suggesting that they could be suitable as potential diagnostic biomarkers for LUSC. Moreover, hierarchical clustering analysis of the DNA methylation data identified two tumor subgroups, one of which showed increased DNA methylation. Conclusions Collectively, these results suggest that DNA methylation plays critical roles in lung tumorigenesis and may potentially be proposed as a diagnostic biomarker. Trial registration ChiCTR-RCC-12002830 Date of registration: 2012–12-17. |
| first_indexed | 2024-12-11T01:15:56Z |
| format | Article |
| id | doaj.art-cd231a4234424f7291ce26e75eb53ac4 |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-12-11T01:15:56Z |
| publishDate | 2017-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-cd231a4234424f7291ce26e75eb53ac42022-12-22T01:25:53ZengBMCBMC Genomics1471-21642017-11-0118111210.1186/s12864-017-4223-3Genome-wide DNA methylation profiling reveals novel epigenetic signatures in squamous cell lung cancerYuan-Xiang Shi0Ying Wang1Xi Li2Wei Zhang3Hong-Hao Zhou4Ji-Ye Yin5Zhao-Qian Liu6Department of Clinical Pharmacology, Xiangya Hospital, Central South UniversityDepartment of Clinical Pharmacology, Xiangya Hospital, Central South UniversityDepartment of Clinical Pharmacology, Xiangya Hospital, Central South UniversityDepartment of Clinical Pharmacology, Xiangya Hospital, Central South UniversityDepartment of Clinical Pharmacology, Xiangya Hospital, Central South UniversityDepartment of Clinical Pharmacology, Xiangya Hospital, Central South UniversityDepartment of Clinical Pharmacology, Xiangya Hospital, Central South UniversityAbstract Background Epigenetic alterations are strongly associated with the development of cancer. The aim of this study was to identify epigenetic pattern in squamous cell lung cancer (LUSC) on a genome-wide scale. Results Here we performed DNA methylation profiling on 24 LUSC and paired non-tumor lung (NTL) tissues by Illumina Human Methylation 450 K BeadArrays, and identified 5214 differentially methylated probes. By integrating DNA methylation and mRNA expression data, 449 aberrantly methylated genes accompanied with altered expression were identified. Ingenuity Pathway analysis highlighted these genes which were closely related to the carcinogenesis of LUSC, such as ERK family, NFKB signaling pathway, Hedgehog signaling pathway, providing new clues for understanding the molecular mechanisms of LUSC pathogenesis. To verify the results of high-throughput screening, we used 56 paired independent tissues for clinical validation by pyrosequencing. Subsequently, another 343 tumor tissues from the Cancer Genome Atlas (TCGA) database were utilized for further validation. Then, we identified a panel of DNA methylation biomarkers (CLDN1, TP63, TBX5, TCF21, ADHFE1 and HNF1B) in LUSC. Furthermore, we performed receiver operating characteristics (ROC) analysis to assess the performance of biomarkers individually, suggesting that they could be suitable as potential diagnostic biomarkers for LUSC. Moreover, hierarchical clustering analysis of the DNA methylation data identified two tumor subgroups, one of which showed increased DNA methylation. Conclusions Collectively, these results suggest that DNA methylation plays critical roles in lung tumorigenesis and may potentially be proposed as a diagnostic biomarker. Trial registration ChiCTR-RCC-12002830 Date of registration: 2012–12-17.http://link.springer.com/article/10.1186/s12864-017-4223-3Lung cancerDNA methylationBiomarkerDiagnosisEpigenetics |
| spellingShingle | Yuan-Xiang Shi Ying Wang Xi Li Wei Zhang Hong-Hao Zhou Ji-Ye Yin Zhao-Qian Liu Genome-wide DNA methylation profiling reveals novel epigenetic signatures in squamous cell lung cancer BMC Genomics Lung cancer DNA methylation Biomarker Diagnosis Epigenetics |
| title | Genome-wide DNA methylation profiling reveals novel epigenetic signatures in squamous cell lung cancer |
| title_full | Genome-wide DNA methylation profiling reveals novel epigenetic signatures in squamous cell lung cancer |
| title_fullStr | Genome-wide DNA methylation profiling reveals novel epigenetic signatures in squamous cell lung cancer |
| title_full_unstemmed | Genome-wide DNA methylation profiling reveals novel epigenetic signatures in squamous cell lung cancer |
| title_short | Genome-wide DNA methylation profiling reveals novel epigenetic signatures in squamous cell lung cancer |
| title_sort | genome wide dna methylation profiling reveals novel epigenetic signatures in squamous cell lung cancer |
| topic | Lung cancer DNA methylation Biomarker Diagnosis Epigenetics |
| url | http://link.springer.com/article/10.1186/s12864-017-4223-3 |
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