Epigenomic analysis of lung adenocarcinoma reveals novel DNA methylation patterns associated with smoking

Figures & data

Figure 1 Differences in global DNA methylation pattern in lung cancer between smokers and nonsmokers. The global DNA methylation pattern in normal lung tissues from smokers (SLT) was compared with that from nonsmokers (NSLT), producing 90 differentially methylated regions. The global DNA methylation pattern of lung tumor tissues from smokers (STT) was compared with that from nonsmokers (NSTT), resulting in 137 differentially methylated regions. Twenty-seven loci can be found in both result sets. The numbers of hypermethylation and hypomethylation loci are also shown. Abbreviation: vs, versus.

Figure 2 Hypothesized model of smoking-induced lung cancer based on our data.

Table 1 Pathways enriched with differentially methylated genes from the comparison between normal lung tissues from smokers and nonsmokers

Category	Term	Count	%	P
GOTERM_BP_FAT	GO:0006006∼glucose metabolic process	4	7.843137255	0.011044244
GOTERM_MF_FAT	GO:0004689∼phosphorylase kinase activity	2	3.921568627	0.014170587
GOTERM_MF_FAT	GO:0004221∼ubiquitin thiolesterase activity	3	5.882352941	0.019246991
GOTERM_BP_FAT	GO:0019318∼hexose metabolic process	4	7.843137255	0.0202083
GOTERM_BP_FAT	GO:0005996∼monosaccharide metabolic process	4	7.843137255	0.029419949
GOTERM_MF_FAT	GO:0016790∼thiolester hydrolase activity	3	5.882352941	0.034057248
GOTERM_MF_FAT	GO:0000166∼nucleotide binding	12	23.52941176	0.04365391
GOTERM_MF_FAT	GO:0048487∼beta-tubulin binding	2	3.921568627	0.044661571

Table 2 Pathway enrichment analysis for smoking-induced lung cancer-specific differentially methylated genes

Term	Count	%	P
GO:0003700∼transcription factor activity	10	27.77777778	0.000326
GO:0019932∼second messenger-mediated signaling	5	13.88888889	0.001931974
GO:0043565∼sequence-specific DNA binding	7	19.44444444	0.00275705
GO:0048168∼regulation of neuronal synaptic plasticity	3	8.333333333	0.003050078
GO:0050804∼regulation of synaptic transmission	4	11.11111111	0.003636035
GO:0051969∼regulation of transmission of nerve impulse	4	11.11111111	0.004521842
GO:0031644∼regulation of neurologic system process	4	11.11111111	0.005055558
GO:0003677∼DNA binding	13	36.11111111	0.005249171
GO:0030528∼transcription regulator activity	10	27.77777778	0.007137687
GO:0048167∼regulation of synaptic plasticity	3	8.333333333	0.009379318
GO:0003002∼regionalization	4	11.11111111	0.010129184
GO:0006325∼chromatin organization	5	13.88888889	0.010398849
GO:0006334∼nucleosome assembly	3	8.333333333	0.015765103
GO:0031497∼chromatin assembly	3	8.333333333	0.016846638
GO:0030182∼neuron differentiation	5	13.88888889	0.017077758
GO:0048015∼phosphoinositide-mediated signaling	3	8.333333333	0.017214047
GO:0065004∼protein-DNA complex assembly	3	8.333333333	0.018336737
GO:0034728∼nucleosome organization	3	8.333333333	0.019102083
GO:0007389∼pattern specification process	4	11.11111111	0.022739147
GO:0051276∼chromosome organization	5	13.88888889	0.023859659
GO:0006323∼DNA packaging	3	8.333333333	0.029291461
GO:0044057∼regulation of system process	4	11.11111111	0.033103168
GO:0006333∼chromatin assembly or disassembly	3	8.333333333	0.03405299
GO:0034622∼cellular macromolecular complex assembly	4	11.11111111	0.035597851
GO:0048666∼neuron development	4	11.11111111	0.041790392
GO:0006355∼regulation of transcription, DNA-dependent	9	25.00000000	0.042198386
GO:0044093∼positive regulation of molecular function	5	13.88888889	0.043420144
GO:0051252∼regulation of RNA metabolic process	9	25.00000000	0.047283874
GO:0034621∼cellular macromolecular complex subunit organization	4	11.11111111	0.04750734

Figure 3 Diagnostic model for classifying smoking-associated lung cancer and nonsmoking lung cancer.

Notes: Classification accuracy is shown with the horizontal axis represents the individual samples grouped according to the disease class whereas the vertical axis represents the predicted classes. Black denotes nonsmokers and red denotes smokers.
Abbreviations: PC, principal component; Sensit, sensitivity; specif, specificity.