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. 2013 Dec 19;135(2):319–334. doi: 10.1002/ijc.28684

Table 3.

Genes for which DNA methylation levels were hallmarks for Clusters I, II and III in the learning cohort

(A) Hallmark genes for Cluster I
Target ID 1 Chrom2 Position3 Gene symbol DNA methylation level in non-cancerous lung tissue (N) samples4 (mean ± SD) p-Value of Welch's t-test (I vs. II and III)5 Δβ (I-II and III)6 p-Value of Jonckheere–Terpstra trend test in I7
Cluster I Cluster II Cluster III
cg20249919 15 102,029,706 PCSK6 0.091 ± 0.188 −0.047 ± 0.109 −0.070 ± 0.125 9.28 × 10−5 0.153 6.51 × 10−4 (Hyper)
cg23349790 1 18,434,576 IGSF21 0.114 ± 0.133 −0.011 ± 0.111 −0.032 ± 0.108 2.41 × 10−6 0.139 4.43 × 10−9 (Hyper)
cg22285621 11 67,071,322 SSH3 0.103 ± 0.116 −0.031 ± 0.075 −0.033 ± 0.082 2.32 × 10−7 0.136 3.69 × 10−7 (Hyper)
cg15433631 5 2,751,541 IRX2 0.123 ± 0.083 −0.007 ± 0.073 0.000 ± 0.070 8.88 × 10−10 0.125 6.60 × 10−8 (Hyper)
cg21949305 22 24,828,655 ADORA2A,CYTSA 0.109 ± 0.053 −0.015 ± 0.040 −0.010 ± 0.052 2.91 × 10−15 0.121 0 (Hyper)
cg10942056 1 223,101,848 DISP1 0.095 ± 0.059 −0.027 ± 0.039 −0.026 ± 0.048 1.59 × 10−13 0.121 4.05 × 10−13 (Hyper)
cg15149645 16 28,550,619 NUPR1 0.090 ± 0.067 −0.023 ± 0.044 −0.033 ± 0.058 7.39 × 10−12 0.12 1.36 × 10−12 (Hyper)
cg06954481 2 237,076,497 GBX2 0.096 ± 0.111 −0.012 ± 0.051 −0.029 ± 0.052 1.02 × 10−6 0.119 1.25 × 10−7 (Hyper)
cg21250978 7 106,684,541 PRKAR2B 0.088 ± 0.060 −0.026 ± 0.044 −0.031 ± 0.056 4.25 × 10−13 0.118 6.13 × 10−9 (Hyper)
cg22418909 8 41,166,738 SFRP1 0.091 ± 0.082 −0.023 ± 0.055 −0.029 ± 0.052 2.38 × 10−9 0.118 1.22 × 10−10 (Hyper)
cg26200585 19 40,919,245 PRX 0.099 ± 0.059 −0.019 ± 0.040 −0.019 ± 0.054 2.44 × 10−13 0.118 0 (Hyper)
cg24396745 15 73,660,614 HCN4 0.096 ± 0.098 −0.022 ± 0.073 −0.015 ± 0.089 3.31 × 10−7 0.114 1.96 × 10−8 (Hyper)
cg04330449 5 134,871,166 NEUROG1 0.098 ± 0.080 −0.001 ± 0.061 −0.019 ± 0.051 5.89 × 10−9 0.111 1.08 × 10−13 (Hyper)
cg19589427 1 173,019,720 TNFSF18 0.076 ± 0.073 −0.036 ± 0.039 −0.032 ± 0.051 9.08 × 10−10 0.11 7.78 × 10−10 (Hyper)
cg16731240 19 52,391,250 ZNF577 0.090 ± 0.105 −0.015 ± 0.072 −0.022 ± 0.061 1.87 × 10−6 0.11 0 (Hyper)
cg03544320 4 5,894,691 CRMP1 0.088 ± 0.108 −0.016 ± 0.105 −0.022 ± 0.101 7.22 × 10−6 0.108 1.61 × 10−10 (Hyper)
cg12864235 5 27,038,782 CDH9 0.092 ± 0.059 −0.011 ± 0.037 −0.018 ± 0.040 3.56 × 10−12 0.108 2.37 × 10−13 (Hyper)
cg15898840 7 45,960,834 IGFBP3 0.102 ± 0.095 −0.001 ± 0.052 −0.008 ± 0.058 4.67 × 10−7 0.107 2.02 × 10−8 (Hyper)
cg08044694 19 15,391,927 BRD4 0.068 ± 0.072 −0.029 ± 0.034 −0.044 ± 0.042 1.55 × 10−9 0.107 1.76 × 10−8 (Hyper)
cg03734874 14 105,071,382 TMEM179 0.099 ± 0.068 0.001 ± 0.056 −0.012 ± 0.055 3.06 × 10−10 0.106 4.39 × 10−13 (Hyper)
cg10599444 14 23,305,941 MMP14 0.064 ± 0.065 −0.039 ± 0.040 −0.044 ± 0.056 8.35 × 10−11 0.106 7.42 × 10−7 (Hyper)
cg24133115 6 166,075,520 PDE10A 0.096 ± 0.071 −0.007 ± 0.054 −0.010 ± 0.046 1.50 × 10−9 0.105 9.66 × 10−10 (Hyper)
cg12594641 2 150,187,223 LYPD6 0.111 ± 0.064 0.011 ± 0.071 0.004 ± 0.061 1.05 × 10−10 0.105 6.56 × 10−7 (Hyper)
cg05724065 7 56,160,528 PHKG1 0.082 ± 0.053 −0.017 ± 0.029 −0.026 ± 0.044 3.01 × 10−13 0.105 4.43 × 10−11 (Hyper)
cg19466563 4 88,450,506 SPARCL1 0.081 ± 0.053 −0.018 ± 0.027 −0.027 ± 0.042 4.93 × 10−13 0.104 0 (Hyper)
cg24433189 16 1,128,689 SSTR5 0.092 ± 0.056 −0.005 ± 0.052 −0.015 ± 0.064 2.58 × 10−12 0.104 9.78 × 10−9 (Hyper)
cg24453664 11 33,758,413 CD59 0.069 ± 0.066 −0.031 ± 0.033 −0.036 ± 0.046 3.23 × 10−10 0.103 9.78 × 10−9 (Hyper)
cg26609631 13 28,366,814 GSX1 0.077 ± 0.081 −0.025 ± 0.063 −0.026 ± 0.057 4.72 × 10−8 0.103 1.73 × 10−11 (Hyper)
cg10604646 1 163,172,649 RGS5 0.086 ± 0.041 −0.029 ± 0.059 −0.009 ± 0.060 4.09 × 10−17 0.102 2.68 × 10−14 (Hyper)
cg03355526 5 178,368,415 ZNF454 0.073 ± 0.070 −0.024 ± 0.043 −0.030 ± 0.061 2.48 × 10−9 0.101 9.13 × 10−13 (Hyper)
cg27096144 5 174,151,779 MSX2 0.074 ± 0.078 −0.020 ± 0.054 −0.030 ± 0.056 3.60 × 10−8 0.101 2.11 × 10−7 (Hyper)
cg15520279 2 176,995,088 HOXD8 0.095 ± 0.083 0.008 ± 0.048 −0.013 ± 0.046 1.06 × 10−7 0.1 1.30 × 10−13 (Hyper)
cg11733245 10 6,104,312 IL2RA −0.112 ± 0.066 −0.001 ± 0.028 −0.016 ± 0.050 5.58 × 10−10 −0.101 8.03 × 10−13 (Hypo)
cg22325572 1 111,416,181 CD53 −0.102 ± 0.062 0.013 ± 0.035 −0.007 ± 0.048 9.63 × 10−11 −0.102 3.52 × 10−12 (Hypo)
cg15691199 14 23,589,419 CEBPE −0.102 ± 0.061 0.006 ± 0.033 −0.003 ± 0.052 4.72 × 10−11 −0.102 1.33 × 10−9 (Hypo)
cg16927606 19 36,233,324 U2AF1L4 −0.086 ± 0.048 0.013 ± 0.028 0.018 ± 0.044 3.10 × 10−14 −0.103 1.79 × 10−8 (Hypo)
cg16240480 1 236,557,473 EDARADD −0.128 ± 0.064 −0.005 ± 0.039 −0.030 ± 0.049 7.69 × 10−11 −0.106 1.59 × 10−9 (Hypo)
cg05596756 12 47,610,220 FAM113B −0.102 ± 0.060 0.009 ± 0.029 0.016 ± 0.047 8.28 × 10−13 −0.116 1.53 × 10−10 (Hypo)
cg08040471 17 80,407,779 C17orf62 −0.116 ± 0.067 0.008 ± 0.036 0.004 ± 0.047 6.99 × 10−12 −0.121 5.63 × 10−11 (Hypo)
cg20622019 20 43,279,793 ADA −0.108 ± 0.072 0.020 ± 0.043 0.012 ± 0.042 3.92 × 10−11 −0.123 1.56 × 10−13 (Hypo)
cg05109049 17 29,641,333 EVI2B −0.141 ± 0.081 0.007 ± 0.050 −0.020 ± 0.063 1.98 × 10−10 −0.13 2.31 × 10−14 (Hypo)
cg07973967 17 62,009,607 CD79B −0.125 ± 0.061 0.016 ± 0.047 0.002 ± 0.056 2.00 × 10−14 −0.132 2.81 × 10−11 (Hypo)
(B) Hallmark genes for Cluster II
Target ID8 Chrom9 Position10 Gene symbol DNA methylation level in non-cancerous lung tissue (N) samples11 (mean ± SD) p-value of Welch's t-test (II vs. I and III)12 Δβ (II-I and III) 13 p-value of Jonckheere–Terpstra trend test in II14
Cluster I Cluster II Cluster III
cg14074641 16 48,181,753 ABCC12 −0.002 ± 0.091 0.025 ± 0.054 −0.109 ± 0.105 1.01 × 10−10 0.101 7.05 × 10−2 (Hyper)
(C) Hallmark genes for Cluster III
Target ID 15 Chrom16 Position17 Gene symbol DNA methylation level in non-cancerous lung tissue (N) samples18 (mean ± SD) p-Value of Welch's t-test (III vs. I and II)19 Δβ (III-I and II) 20 p-Value of Jonckheere–Terpstra trend test in III21
Cluster I Cluster II Cluster III
cg26606064 11 125,439,070 EI24 0.020 ± 0.083 0.008 ± 0.064 0.115 ± 0.105 8.57 × 10−10 0.101 2.36 × 10−2 (Hyper)
cg17872476 10 114,205,654 VTI1A −0.034 ± 0.091 −0.035 ± 0.060 −0.137 ± 0.120 1.61 × 10−8 −0.102 1.51 × 10−2 (Hypo)
cg21063899 13 78,109,801 SCEL 0.033 ± 0.088 0.013 ± 0.054 −0.081 ± 0.086 3.06 × 10−12 −0.103 1.47 × 10−9 (Hypo)
cg14074641 16 48,181,753 ABCC12 −0.002 ± 0.091 0.025 ± 0.054 −0.109 ± 0.105 1.40 × 10−12 −0.121 2.44 × 10−1 (Hypo)
1

Probe ID for the Infinium HumanMethylation27 Bead Array.

2

Chromosome.

3

National Center for Biotechnology Information (NCBI) Database (Genome Build 37).

4

ΔβN-averageC.

5

Average βN–C in Cluster I versus average βN–C in Clusters II and III. Such p values were calculated to reveal the hallmark genes of Cluster I that showed DNA methylation statuses significantly different in their N samples in comparison with N samples from other clusters (Clusters II and III).

6

Average βN–C in Cluster I minus average βN–C in Clusters II and III. If Δβ (I-II and III) was more than 0.1, N samples in Cluster I were considered to show DNA hypermethylation relative to N samples in other clusters, and if Δβ (I-II and III) was less than −0.1, N samples in Cluster I were considered to show DNA hypomethylation relative to N samples in other clusters.

7

Stepwise DNA hypermethylation (Hyper) and hypomethylation (Hypo) from normal lung tissue samples to N samples, and then to tumorous tissue samples in Cluster I.

8

Probe ID for the Infinium HumanMethylation27 Bead Array.

9

Chromosome.

10

National Center for Biotechnology Information (NCBI) Database (Genome Build 37).

11

Δβ N-averageC.

12

Average βN–C in Cluster II versus average βN–C in Clusters I and III. Such p value was calculated to reveal the hallmark gene of Cluster II that showed DNA methylation status significantly different in their N samples in comparison with N samples from other clusters (Clusters I and III).

13

Average βN–C in Cluster II minus average βN–C in Clusters I and III. If Δβ (II−I and III) was more than 0.1, N samples in Cluster II were considered to show DNA hypermethylation relative to N samples in other clusters.

14

Stepwise DNA hypermethylation (Hyper) and hypomethylation (Hypo) from normal lung tissue samples to N samples, and then to tumorous tissue samples in Cluster II.

15

Probe ID for the Infinium HumanMethylation27 Bead Array.

16

Chromosome.

17

National Center for Biotechnology Information (NCBI) Database (Genome Build 37).

18

Δβ N-averageC.

19

Average βN–C in Cluster III versus average βN–C in Clusters I and II. Such p values were calculated to reveal the hallmark gene of Cluster III that showed DNA methylation statuses significantly different in their N samples in comparison with N samples from other clusters (Clusters I and II).

20

Average βN–C in Cluster III minus average βN–C in Clusters I and II. If Δβ (III-I and II) was more than 0.1, N samples in Cluster III were considered to show DNA hypermethylation relative to N samples in other clusters and if Δβ (III-I and II) was less than −0.1, N samples in Cluster III were considered to show DNA hypomethylation relative to N samples in other clusters.

21

Stepwise DNA hypermethylation (Hyper) and hypomethylation (Hypo) from normal lung tissue samples to N samples, and then to tumorous tissue samples in Cluster III.