Triple-layer dissection of the lung adenocarcinoma transcriptome - regulation at the gene, transcript, and exon levels

Hsu, Min-Kung; Wu, I-Ching; Cheng, Chieh-Fang; Su, Jen-Liang; Hsieh, Chang-Huain; Lin, Yeong-Shin; Chen, Feng‐Chi

doi:10.18632/oncotarget.4810

Cited by 16 publications

(15 citation statements)

References 66 publications

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“…CELSR3 was found to be highly expressed in ovarian cancer, 4 and hypermethylated in primary oral squamous cell carcinoma, and might be used as a biomarker in OSCC prognostication 10 and small intestinal neuroendocrine tumor. 5 TNXB was reported to be important for the tumorigenesis of lung adenocarcinoma, 6 and was validated as a promising biomarker for early metastasis of breast cancer. 7 TRPM2 was reported to be a potential target of the selective treatment of prostate cancer 11 and was suggested to be a potential therapeutic target in breast cancer.…”

Section: Resultsmentioning

confidence: 99%

Integrative analysis with expanded DNA methylation data reveals common key regulators and pathways in cancers

Fan

Tang

et al. 2019

npj Genomic Med

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The integration of genomic and DNA methylation data has been demonstrated as a powerful strategy in understanding cancer mechanisms and identifying therapeutic targets. The TCGA consortium has mapped DNA methylation in thousands of cancer samples using Illumina Infinium Human Methylation 450 K BeadChip (Illumina 450 K array) that only covers about 1.5% of CpGs in the human genome. Therefore, increasing the coverage of the DNA methylome would significantly leverage the usage of the TCGA data. Here, we present a new model called EAGLING that can expand the Illumina 450 K array data 18 times to cover about 30% of the CpGs in the human genome. We applied it to analyze 13 cancers in TCGA. By integrating the expanded methylation, gene expression, and somatic mutation data, we identified the genes showing differential patterns in each of the 13 cancers. Many of the triple-evidenced genes identified in majority of the cancers are biomarkers or potential biomarkers. Pan-cancer analysis also revealed the pathways in which the triple-evidenced genes are enriched, which include well known ones as well as new ones, such as axonal guidance signaling pathway and pathways related to inflammatory processing or inflammation response. Triple-evidenced genes, particularly TNXB, RRM2, CELSR3, SLC16A3, FANCI, MMP9, MMP11, SIK1, and TRIM59 showed superior predictive power in both tumor diagnosis and prognosis. These results have demonstrated that the integrative analysis using the expanded methylation data is powerful in identifying critical genes/pathways that may serve as new therapeutic targets.

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Section: Resultsmentioning

confidence: 99%

Integrative analysis with expanded DNA methylation data reveals common key regulators and pathways in cancers

Fan

Tang

et al. 2019

npj Genomic Med

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“…Furthermore, it has been demonstrated that silencing of TNX genes promoted malignant transformation in mice [ 32 ]. In addition, TNX genes also could be considered as candidate genes for the distinction between tumor and normal groups in lung adenocarcinoma [ 33 ]. Here, aberrant TNXB DNA methylation was first reported in EC.…”

Section: Discussionmentioning

confidence: 99%

Identification of DNA methylation associated gene signatures in endometrial cancer via integrated analysis of DNA methylation and gene expression systematically

et al. 2017

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ObjectiveEndometrial cancer (EC) is a common gynecologic cancer worldwide. However, the pathogenesis of EC has not been epigenetically elucidated. Here, this study aims to describe the DNA methylation profile and identify favorable gene signatures highly associated with aberrant DNA methylation changes in EC.MethodsThe data regarding DNA methylation and gene expression were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially methylated CpG sites (DMCs), differentially methylated regions (DMRs), and differentially expressed genes (DEGs) were identified, and the relationship between the 2 omics was further analyzed. In addition, weighted CpG site co-methylation network (WCCN) was constructed followed by an integrated analysis of DNA methylation and gene expression data.ResultsFour hundred thirty-one tumor tissues and 46 tissues adjacent tumor of EC patients were analyzed. One thousand one hundred thirty-five DMCs (merging to 10 DMRs), and 1,488 DEGs were obtained between tumor and normal groups, respectively. One hundred forty-eight DMCs-DEGs correlated pairs and 13 regional DMCs-DEGs pairs were obtained. Interestingly, we found that some hub genes in 2 modules among 8 modules of WCCN analysis were down-regulated in tumor samples. Furthermore, protocadherins (PCDHs) clusters, DDP6, TNXB, and ZNF154 were identified as novel deregulated genes with altered methylation in EC.ConclusionBased on the analysis of DNA methylation in a systematic view, the potential long-range epigenetic silencing (LRES) composed of PCDHs was reported in ECs for the first time. PCDHs clusters, DDP6, and TNXB were firstly found to be associated with tumorigenesis, and may be novel candidate biomarkers for EC.

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“…The triple-evidenced genes represent the genes that are differentially methylated, differentially expressed and associated with somatic mutation. We found that the triple-evidenced genes shared by a majority of the 13 cancers include many previously identified biomarkers or therapeutic targets [4][5][6][7] . These triple-evidenced genes are enriched in numerous pathways, suggesting possible new targets for therapeutics.…”

Section: Introductionmentioning

confidence: 84%

“…CELSR3 was found to be highly expressed in ovarian cancer 4 , and hypermethylated in primary oral squamous cell carcinoma, and might be used as a biomarker in OSCC prognostication 10 and small intestinal neuroendocrine tumor 5 . TNXB was reported to be important for the tumorigenesis of lung adenocarcinoma 6 , and was validated as a promising biomarker for early metastasis of breast cancer 7 .TRPM2 was reported to be a potential target of the selective treatment of prostate cancer 11 and was suggested to be a potential therapeutic target in breast cancer 12 . TRIP13 promoted early steps of the DNA double-strand break repair and its presence was associated with progression in prostate cancer and squamous cell carcinoma of the head and neck 13,14 .…”

Section: Identification Of Triple-evidenced Genesmentioning

confidence: 99%

Integrative analysis with expanded DNA methylation data reveals common key regulators and pathways in cancers

Fan

Tang

Li³

et al. 2018

Preprint

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The integration of genomic and DNA methylation data has been demonstrated as a powerful strategy in understanding cancer mechanisms and identifying therapeutic targets. The TCGA consortium has mapped DNA methylation in thousands of cancer samples using Illumina Infinium Human Methylation 450K BeadChip (Illumina 450K array) that only covers about 1.5% of CpGs in the human genome. Therefore, increasing the coverage of the DNA methylome would significantly leverage the usage of the TCGA data. Here, we present a new model called EAGLING that can expand the Illumina 450K array data 18 times to cover about 30% of the CpGs in the human genome. We applied it to analyze 13 cancers in TCGA. By integrating the expanded methylation, gene expression and somatic mutation data, we identified the genes showing differential patterns in each of the 13 cancers. Many of the triple-evidenced genes identified in the majority of the cancers are biomarkers or potential biomarkers. Pan-cancer analysis also revealed the pathways in which the triple-evidenced genes are enriched, which include well known ones as well as new ones such as axonal guidance signaling pathway and pathways related to inflammatory processing or inflammation response. Triple-evidenced genes, particularly TNXB, RRM2, CELSR3, SLC16A3, FANCI, MMP9, MMP11, SIK1, TRIM59, showed superior predictive power in both tumor diagnosis and prognosis. These results have demonstrated that the integrative analysis using the expanded methylation data is powerful in identifying critical genes/pathways that may serve as new therapeutic targets.

show abstract

Triple-layer dissection of the lung adenocarcinoma transcriptome - regulation at the gene, transcript, and exon levels

Cited by 16 publications

References 66 publications

Integrative analysis with expanded DNA methylation data reveals common key regulators and pathways in cancers

Integrative analysis with expanded DNA methylation data reveals common key regulators and pathways in cancers

Identification of DNA methylation associated gene signatures in endometrial cancer via integrated analysis of DNA methylation and gene expression systematically

Integrative analysis with expanded DNA methylation data reveals common key regulators and pathways in cancers

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