Genome-wide analysis of DNA methylation and their associations with long noncoding RNA/mRNA expression in non-small-cell lung cancer.

AIM The goal of this study is to identify differentially methylated (DM) loci associated with long noncoding RNA (lncRNA)/mRNA expression in non-small-cell lung cancer (NSCLC). MATERIALS & METHODS Microarrays were used to interrogate genome-wide methylation and expression of lncRNA/mRNA in NSCLC. RESULTS We identified 113,644 DM loci between tumors and adjacent tissues. Among them, 26,310 DM loci were associated with 1685 differentially expressed genes, and 839 genes had significant correlations between methylation and expression, of which 26 hypermethylated loci in transcription start site 200 were correlated with low gene expression. We validated the correlations between methylation and expression in five genes (CDO1, C2orf40, SCARF1, ZFP106 and IFFO1) using pyrosequencing and quantitative polymerase chain reaction. We also found significant correlations between lncRNAs and mRNAs, and validated four of the correlations with quantitative polymerase chain reaction. CONCLUSION Integrated analysis of genome-wide DNA methylation and lncRNA/mRNA expression allows us to identify new DM loci-correlated with gene expression in NSCLC.

[1]  Dirk Schadendorf,et al.  Epigenetic deregulation of TCF21 inhibits metastasis suppressor KISS1 in metastatic melanoma. , 2011, Carcinogenesis.

[2]  G. Lang,et al.  Genome-wide CpG island methylation analyses in non-small cell lung cancer patients. , 2013, Carcinogenesis.

[3]  Ludmila V. Danilova,et al.  Frequent Inactivation of Cysteine Dioxygenase Type 1 Contributes to Survival of Breast Cancer Cells and Resistance to Anthracyclines , 2013, Clinical Cancer Research.

[4]  J. Foekens,et al.  RESEARCH ARTICLE Open Access Research article CDO1 Promoter Methylation is a Biomarker for Outcome Prediction of Anthracycline Treated, Estrogen Receptor-Positive, Lymph Node-Positive Breast Cancer Patients , 2022 .

[5]  K. Tozawa,et al.  GPX2 overexpression is involved in cell proliferation and prognosis of castration-resistant prostate cancer. , 2014, Carcinogenesis.

[6]  C. Plass,et al.  Long noncoding RNA TARID directs demethylation and activation of the tumor suppressor TCF21 via GADD45A. , 2014, Molecular cell.

[7]  J. Adrian Gillet,et al.  Cancer diagnosis and prognosis , 1969 .

[8]  D. Dai,et al.  Protein expression and promoter methylation of the candidate biomarker TCF21 in gastric cancer , 2015, Journal of Cancer Research and Clinical Oncology.

[9]  Jingcheng Yang,et al.  Analysis of lncRNA expression profiles in non-small cell lung cancers (NSCLC) and their clinical subtypes. , 2014, Lung cancer.

[10]  Xiao-shu Hu,et al.  Expression of esophageal carcinoma related gene 4 (ECRG4) and its clinical significance in prognosis of esophageal carcinoma. , 2015, International journal of clinical and experimental pathology.

[11]  E. Petricoin,et al.  Integrated Genomic and Epigenomic Analysis of Breast Cancer Brain Metastasis , 2014, PloS one.

[12]  J. Mao,et al.  C2ORF40 suppresses breast cancer cell proliferation and invasion through modulating expression of M phase cell cycle genes , 2013, Epigenetics.

[13]  C. Rudack,et al.  Protein expression and promoter methylation of the candidate biomarker TCF21 in head and neck squamous cell carcinoma , 2013, Cellular Oncology.

[14]  J. Herman,et al.  Functional Identification of Cancer-Specific Methylation of CDO1, HOXA9, and TAC1 for the Diagnosis of Lung Cancer , 2014, Clinical Cancer Research.

[15]  Kang Jin Jeong,et al.  Genome-wide combination profiling of DNA copy number and methylation for deciphering biomarkers in non-small cell lung cancer patients. , 2011, Cancer letters.

[16]  N. Hacohen,et al.  The scavenger receptor SCARF 1 mediates the clearance of apoptotic cells and prevents autoimmunity , 2022 .

[17]  I. B. Borel Rinkes,et al.  GPx2 suppression of H2O2 stress links the formation of differentiated tumor mass to metastatic capacity in colorectal cancer. , 2014, Cancer research.

[18]  B. Karlan,et al.  A Collagen-Remodeling Gene Signature Regulated by TGF-β Signaling Is Associated with Metastasis and Poor Survival in Serous Ovarian Cancer , 2013, Clinical Cancer Research.

[19]  H. Kędzierska,et al.  Expression of Genes Involved in Cellular Adhesion and Extracellular Matrix Remodeling Correlates with Poor Survival of Patients with Renal Cancer. , 2016, The Journal of urology.

[20]  R. Lothe,et al.  TCF21 and PCDH17 methylation: An innovative panel of biomarkers for a simultaneous detection of urological cancers , 2011, Epigenetics.

[21]  J. Déjardin,et al.  End-targeting proteomics of isolated chromatin segments of a mammalian ribosomal RNA gene promoter , 2015, Nature Communications.

[22]  Roberto Incitti,et al.  Aberrant methylation of NPY, PENK, and WIF1 as a promising marker for blood-based diagnosis of colorectal cancer , 2013, BMC Cancer.

[23]  Hiromu Suzuki,et al.  A genomic screen for long noncoding RNA genes epigenetically silenced by aberrant DNA methylation in colorectal cancer , 2016, Scientific Reports.

[24]  J. Tost,et al.  Complete pipeline for Infinium(®) Human Methylation 450K BeadChip data processing using subset quantile normalization for accurate DNA methylation estimation. , 2012, Epigenomics.

[25]  Jin-Haeng Chung,et al.  DNA methylation profile during multistage progression of pulmonary adenocarcinomas , 2011, Virchows Archiv.

[26]  Yair Lotan,et al.  Detection of Bladder Cancer Using Novel DNA Methylation Biomarkers in Urine Sediments , 2011, Cancer Epidemiology, Biomarkers & Prevention.

[27]  Y. Xi,et al.  Validation of biomarkers associated with 5-fluorouracil and thymidylate synthase in colorectal cancer. , 2008, Oncology reports.

[28]  P. Laird,et al.  Genome-Scale Screen for DNA Methylation-Based Detection Markers for Ovarian Cancer , 2011, PloS one.

[29]  S. Ropero,et al.  A DNA hypermethylation profile reveals new potential biomarkers for the evaluation of prognosis in urothelial bladder cancer , 2017, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[30]  Z. Cai,et al.  Down-regulation of TCF21 is associated with poor survival in clear cell renal cell carcinoma. , 2012, Neoplasma.

[31]  Peiyong Jiang,et al.  Noninvasive detection of cancer-associated genome-wide hypomethylation and copy number aberrations by plasma DNA bisulfite sequencing , 2013, Proceedings of the National Academy of Sciences.

[32]  J. Hesketh,et al.  Selenium alters miRNA profile in an intestinal cell line: evidence that miR-185 regulates expression of GPX2 and SEPSH2. , 2013, Molecular nutrition & food research.

[33]  B. Qian,et al.  Analysis of Microarray Data on Gene Expression and Methylation to Identify Long Non-coding RNAs in Non-small Cell Lung Cancer , 2016, Scientific Reports.

[34]  W. Gerald,et al.  A Genome-Wide Screen for Promoter Methylation in Lung Cancer Identifies Novel Methylation Markers for Multiple Malignancies , 2006, PLoS medicine.

[35]  D. Deng,et al.  Expression of ECRG4, a novel esophageal cancer-related gene, downregulated by CpG island hypermethylation in human esophageal squamous cell carcinoma. , 2003, World journal of gastroenterology.

[36]  Christoph Plass,et al.  Epigenetic regulation of the tumor suppressor gene TCF21 on 6q23-q24 in lung and head and neck cancer. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[37]  Xiao-yan Li,et al.  A novel tumor suppressor gene ECRG4 interacts directly with TMPRSS11A (ECRG1) to inhibit cancer cell growth in esophageal carcinoma , 2011, BMC Cancer.

[38]  D. Spector,et al.  Long noncoding RNAs: functional surprises from the RNA world. , 2009, Genes & development.

[39]  Mihaela Campan,et al.  Identification of a panel of sensitive and specific DNA methylation markers for squamous cell lung cancer , 2008, Molecular Cancer.

[40]  Z. Dong,et al.  Aberrant methylation-mediated downregulation of long noncoding RNA LOC100130476 correlates with malignant progression of esophageal squamous cell carcinoma. , 2016, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[41]  S. Zöchbauer-Müller,et al.  Lung cancer: From single-gene methylation to methylome profiling , 2010, Cancer and Metastasis Reviews.

[42]  B. Stillman,et al.  Orc6 Involved in DNA Replication, Chromosome Segregation, and Cytokinesis , 2002, Science.