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

Table 4.

Correlation between DNA methylation levels of hallmark genes for Clusters I, II and III and the clinicopathological parameters in the validation cohort

(A) Hallmark genes for Cluster I

Target ID 1 Gene symbol DNA methylation level in non-cancerous lung tissue (N) samples2 (mean ± SD)

Pleural anthracosis Emphysematic change Atypical adenomatous hyperplasia Tumor anthracosis




G1 G2-3 p-Value3 Negative Positive p-Value3 Absence Presence p-Value3 Negative Positive p-Value3
cg20249919 PCSK6 −0.126 ± 0.049 −0.049 ± 0.102 1.83×10−2 −0.069 ± 0.067 −0.049 ± 0.131 4.99×10−1 −0.056 ± 0.101 −0.096 ± 0.082 3.57×10−1 −0.077 ± 0.085 −0.047 ± 0.105 3.18×10−1
cg23349790 IGSF21 −0.044 ± 0.101 −0.002 ± 0.100 4.13×10−1 −0.035 ± 0.072 0.028 ± 0.118 3.50×10−2 −0.005 ± 0.101 −0.029 ± 0.086 5.79×10−1 −0.054 ± 0.079 0.017 ± 0.098 1.68×10−2
cg22285621 SSH3 −0.073 ± 0.043 0.002 ± 0.101 1.25×10−2 −0.001 ± 0.077 −0.014 ± 0.121 6.52×10−1 −0.004 ± 0.101 −0.035 ± 0.059 3.41×10−1 −0.015 ± 0.077 0.001 ± 0.106 5.69×10−1
cg15433631 IRX2 −0.041 ± 0.061 0.034 ± 0.074 4.73×10−2 0.025 ± 0.068 0.029 ± 0.083 8.52×10−1 0.026 ± 0.077 0.028 ± 0.056 9.46×10−1 0.010 ± 0.074 0.037 ± 0.072 2.77×10−1
cg21949305 ADORA2A,CYTSA 0.025 ± 0.091 0.026 ± 0.060 9.73×10−1 0.015 ± 0.054 0.039 ± 0.069 1.91×10−1 0.029 ± 0.063 −0.003 ± 0.036 1.28×10−1 −0.004 ± 0.058 0.039 ± 0.061 3.48×10−2
cg10942056 DISP1 0.014 ± 0.088 0.015 ± 0.068 9.71×10−1 0.009 ± 0.062 0.023 ± 0.077 5.00×10−1 0.019 ± 0.071 −0.022 ± 0.027 2.48×10−2 −0.007 ± 0.056 0.026 ± 0.072 1.08×10−1
cg15149645 NUPR1 −0.007 ± 0.124 0.013 ± 0.073 7.37×10−1 0.006 ± 0.070 0.015 ± 0.085 7.06×10−1 0.015 ± 0.079 −0.036 ± 0.022 2.81×10−3 −0.015 ± 0.081 0.021 ± 0.077 1.77×10−1
cg06954481 GBX2 −0.044 ± 0.031 0.013 ± 0.075 9.57×10−3 0.008 ± 0.062 0.003 ± 0.085 7.95×10−1 0.012 ± 0.073 −0.047 ± 0.040 2.27×10−2 −0.012 ± 0.058 0.016 ± 0.078 1.90×10−1
cg21250978 PRKAR2B −0.013 ± 0.092 0.002 ± 0.058 7.44×10−1 −0.010 ± 0.050 0.014 ± 0.070 1.95×10−1 0.005 ± 0.061 −0.037 ± 0.033 4.81×10−2 −0.032 ± 0.058 0.013 ± 0.059 2.63×10−2
cg22418909 SFRP1 −0.043 ± 0.076 0.002 ± 0.058 2.55×10−1 0.000 ± 0.065 −0.003 ± 0.053 8.32×10−1 0.003 ± 0.061 −0.041 ± 0.022 4.86×10−3 −0.020 ± 0.057 0.007 ± 0.060 1.64×10−1
cg26200585 PRX 0.020 ± 0.079 0.015 ± 0.066 8.81×10−1 0.013 ± 0.069 0.016 ± 0.063 8.89×10−1 0.019 ± 0.067 −0.029 ± 0.035 3.48×10−2 −0.006 ± 0.054 0.025 ± 0.070 1.19×10−1
cg24396745 HCN4 −0.056 ± 0.035 0.020 ± 0.072 3.53×10−3 0.017 ± 0.066 0.003 ± 0.079 4.87×10−1 0.015 ± 0.073 −0.025 ± 0.054 1.86×10−1 −0.005 ± 0.074 0.022 ± 0.071 2.60×10−1
cg04330449 NEUROG1 −0.040 ± 0.033 0.010 ± 0.073 2.33×10−2 0.010 ± 0.065 −0.005 ± 0.078 4.52×10−1 0.006 ± 0.072 −0.020 ± 0.056 3.82×10−1 −0.006 ± 0.044 0.012 ± 0.078 3.40×10−1
cg19589427 TNFSF18 −0.008 ± 0.078 −0.010 ± 0.070 9.65×10−1 −0.010 ± 0.078 −0.012 ± 0.057 9.26×10−1 −0.007 ± 0.071 −0.042 ± 0.036 1.10×10−1 −0.040 ± 0.057 0.005 ± 0.069 3.13×10−2
cg16731240 ZNF577 −0.042 ± 0.037 0.014 ± 0.087 2.50×10−2 0.012 ± 0.1000 0.003 ± 0.060 7.02×10−1 0.007 ± 0.086 0.014 ± 0.078 8.48×10−1 −0.015 ± 0.074 0.020 ± 0.087 1.79×10−1
cg03544320 CRMP1 −0.097 ± 0.083 0.018 ± 0.094 3.14×10−2 0.010 ± 0.109 −0.005 ± 0.084 5.67×10−1 0.008 ± 0.102 −0.040 ± 0.036 4.56×10−2 −0.014 ± 0.095 0.019 ± 0.097 3.04×10−1
cg12864235 CDH9 0.032 ± 0.054 0.027 ± 0.057 8.51×10−1 0.025 ± 0.045 0.030 ± 0.066 7.86×10−1 0.031 ± 0.057 −0.004 ± 0.019 1.29×10−2 0.012 ± 0.043 0.034 ± 0.060 1.77×10−1
cg15898840 IGFBP3 −0.043 ± 0.030 0.001 ± 0.057 2.53×10−2 −0.004 ± 0.052 −0.007 ± 0.061 8.16×10−1 −0.002 ± 0.056 −0.036 ± 0.037 1.14×10−1 −0.003 ± 0.044 −0.002 ± 0.060 9.36×10−1
cg08044694 BRD4 −0.067 ± 0.036 −0.020 ± 0.049 3.84×10−2 −0.021 ± 0.046 −0.028 ± 0.053 6.30×10−1 −0.022 ± 0.050 −0.039 ± 0.035 3.55×10−1 −0.041 ± 0.041 −0.017 ± 0.052 1.12×10−1
cg03734874 TMEM179 −0.032 ± 0.034 0.023 ± 0.074 1.62×10−2 0.021 ± 0.076 0.015 ± 0.068 7.56×10−1 0.024 ± 0.072 −0.037 ± 0.039 1.89×10−2 −0.008 ± 0.052 0.030 ± 0.075 5.63×10−2
cg10599444 MMP14 −0.063 ± 0.026 −0.010 ± 0.060 4.85×10−3 −0.008 ± 0.057 −0.023 ± 0.060 3.87×10−1 −0.013 ± 0.060 −0.027 ± 0.041 5.25×10−1 −0.026 ± 0.047 −0.007 ± 0.059 2.66×10−1
cg24133115 PDE10A −0.020 ± 0.025 0.022 ± 0.060 1.58×10−2 0.014 ± 0.059 0.020 ± 0.057 7.02×10−1 0.018 ± 0.060 0.004 ± 0.027 3.88×10−1 0.009 ± 0.037 0.024 ± 0.063 3.25×10−1
cg12594641 LYPD6 −0.024 ± 0.041 0.036 ± 0.068 2.45×10−2 0.021 ± 0.062 0.036 ± 0.075 4.61×10−1 0.029 ± 0.071 0.013 ± 0.038 4.43×10−1 0.025 ± 0.045 0.035 ± 0.075 5.94×10−1
cg05724065 PHKG1 0.016 ± 0.100 0.011 ± 0.057 9.10×10−1 0.014 ± 0.055 0.008 ± 0.067 7.39×10−1 0.016 ± 0.061 −0.032 ± 0.027 1.05×10−2 −0.002 ± 0.066 0.019 ± 0.059 3.33×10−1
cg19466563 SPARCL1 0.018 ± 0.081 0.012 ± 0.055 8.86×10−1 0.007 ± 0.052 0.021 ± 0.060 3.98×10−1 0.019 ± 0.056 −0.035 ± 0.015 4.46×10−5 −0.015 ± 0.047 0.025 ± 0.057 2.24×10−2
cg24433189 SSTR5 0.024 ± 0.075 0.034 ± 0.060 7.96×10−1 0.031 ± 0.052 0.032 ± 0.071 9.63×10−1 0.035 ± 0.062 −0.003 ± 0.027 2.95×10−2 0.026 ± 0.051 0.036 ± 0.065 5.79×10−1
cg24453664 CD59 −0.057 ± 0.039 0.000 ± 0.053 2.44×10−2 −0.002 ± 0.054 −0.009 ± 0.055 6.40×10−1 −0.004 ± 0.054 −0.021 ± 0.050 5.00×10−1 −0.018 ± 0.050 0.001 ± 0.055 2.53×10−1
cg26609631 GSX1 −0.051 ± 0.058 0.006 ± 0.067 9.21×10−2 0.002 ± 0.066 −0.005 ± 0.069 7.29×10−1 0.004 ± 0.068 −0.050 ± 0.025 3.65×10−3 −0.020 ± 0.054 0.010 ± 0.071 1.35×10−1
cg10604646 RGS5 0.038 ± 0.039 0.033 ± 0.058 8.08×10−1 0.013 ± 0.062 0.056 ± 0.041 5.70×10−3 0.037 ± 0.056 −0.014 ± 0.057 1.16×10−1 −0.006 ± 0.063 0.049 ± 0.047 1.07×10−2
cg03355526 ZNF454 −0.061 ± 0.044 0.001 ± 0.075 2.98×10−2 0.003 ± 0.077 −0.012 ± 0.070 4.81×10−1 0.002 ± 0.074 −0.052 ± 0.053 8.77×10−2 −0.007 ± 0.058 0.000 ± 0.078 7.53×10−1
cg27096144 MSX2 −0.066 ± 0.049 0.001 ± 0.063 3.29×10−2 −0.006 ± 0.057 −0.006 ± 0.072 9.95×10−1 −0.003 ± 0.065 −0.026 ± 0.040 2.94×10−1 −0.023 ± 0.055 0.002 ± 0.068 2.05×10−1
cg15520279 HOXD8 −0.021 ± 0.040 0.016 ± 0.070 1.15×10−1 0.015 ± 0.075 0.009 ± 0.056 7.16×10−1 0.014 ± 0.070 −0.006 ± 0.025 2.05×10−1 −0.010 ± 0.038 0.024 ± 0.075 4.76×10−2
cg11733245 IL2RA −0.037 ± 0.042 −0.035 ± 0.051 9.29×10−1 −0.023 ± 0.038 −0.047 ± 0.060 1.10×10−1 −0.035 ± 0.051 −0.013 ± 0.023 1.09×10−1 −0.009 ± 0.035 −0.047 ± 0.050 7.07×10−3
cg22325572 CD53 −0.024 ± 0.083 −0.028 ± 0.058 9.23×10−1 −0.017 ± 0.051 −0.040 ± 0.067 1.90×10−1 −0.029 ± 0.060 −0.008 ± 0.057 4.68×10−1 0.003 ± 0.057 −0.041 ± 0.057 2.96×10−2
cg15691199 CEBPE −0.029 ± 0.080 −0.018 ± 0.064 7.94×10−1 −0.016 ± 0.050 −0.022 ± 0.079 7.79×10−1 −0.022 ± 0.066 0.015 ± 0.021 1.52×10−2 −0.002 ± 0.061 −0.028 ± 0.067 2.28×10−1
cg16927606 U2AF1L4 −0.012 ± 0.079 −0.004 ± 0.054 8.25×10−1 −0.005 ± 0.048 −0.006 ± 0.065 9.54×10−1 −0.010 ± 0.057 0.032 ± 0.025 1.48×10−2 0.009 ± 0.051 −0.012 ± 0.057 2.31×10−1
cg16240480 EDARADD −0.040 ± 0.103 −0.047 ± 0.072 8.91×10−1 −0.032 ± 0.071 −0.062 ± 0.075 1.61×10−1 −0.048 ± 0.074 −0.017 ± 0.070 3.86×10−1 0.001 ± 0.049 −0.066 ± 0.076 1.24×10−3
cg05596756 FAM113B −0.010 ± 0.085 −0.010 ± 0.062 9.92×10−1 0.000 ± 0.052 −0.022 ± 0.073 2.22×10−1 −0.014 ± 0.064 0.026 ± 0.025 2.14×10−2 0.011 ± 0.057 −0.020 ± 0.065 1.30×10−1
cg08040471 C17orf62 0.000 ± 0.073 −0.014 ± 0.066 7.11×10−1 −0.002 ± 0.051 −0.024 ± 0.080 2.80×10−1 −0.015 ± 0.068 0.013 ± 0.029 1.21×10−1 0.019 ± 0.053 −0.027 ± 0.066 2.03×10−2
cg20622019 ADA −0.021 ± 0.073 −0.033 ± 0.068 7.39×10−1 −0.028 ± 0.069 −0.035 ± 0.066 7.31×10−1 −0.036 ± 0.069 0.008 ± 0.021 6.34×10−3 0.002 ± 0.051 −0.047 ± 0.068 1.14×10−2
cg05109049 EVI2B −0.057 ± 0.106 −0.041 ± 0.090 7.56×10−1 −0.023 ± 0.093 −0.062 ± 0.084 1.32×10−1 −0.044 ± 0.090 −0.009 ± 0.102 5.07×10−1 −0.002 ± 0.054 −0.058 ± 0.099 1.72×10−2
cg07973967 CD79B −0.034 ± 0.105 −0.028 ± 0.075 9.16×10−1 −0.017 ± 0.060 −0.042 ± 0.094 2.83×10−1 −0.031 ± 0.080 0.007 ± 0.021 2.06×10−2 −0.007 ± 0.067 −0.039 ± 0.081 1.69×10−1
(B) Hallmark genes for Cluster II and III

Target ID 4 Gene symbol DNA methylation level in non-cancerous lung tissue (N) samples5 (mean ± SD)

Lymphatic invasion Nodal status Pathological Tumor-Node-Metastasis stage



Negative Positive p-Value6 N0 N1 N2-3 p-Value6 IA-IB IIA-IIB IIIA-IV p-Value6
cg26606064 EI24 0.018 ± 0.098 0.098 ± 0.113 3.01 × 10−2 0.004 ± 0.098 0.010 ± 0.094 0.118 ± 0.091 1.27 × 10−3 0.009 ± 0.102 −0.008 ± 0.082 0.118 ± 0.091 1.14 × 10−3
cg17872476 VTI1A −0.035 ± 0.134 −0.126 ± 0.137 4.32 × 10−2 −0.023 ± 0.132 0.022 ± 0.127 −0.149 ± 0.121 5.69 × 10−3 −0.020 ± 0.116 −0.016 ± 0.166 −0.149 ± 0.121 6.70 × 10−3
cg21063899 SCEL −0.043 ± 0.093 −0.109 ± 0.110 6.08 × 10−2 −0.024 ± 0.082 −0.024 ± 0.090 −0.141 ± 0.096 2.81 × 10−4 −0.021 ± 0.089 −0.033 ± 0.062 −0.141 ± 0.096 2.60 × 10−4
cg14074641 ABCC12 −0.017 ± 0.118 −0.083 ± 0.117 8.60 × 10−2 0.005 ± 0.104 −0.006 ± 0.112 −0.118 ± 0.114 2.09 × 10−3 0.000 ± 0.111 0.014 ± 0.084 −0.118 ± 0.114 2.00 × 10−3
1

Probe ID for the Infinium HumanMethylation27 Bead Array.

2

ΔβN-averageC.

3

p values (Welch's t-test) of <0.05 are underlined.

4

Probe ID for the Infinium HumanMethylation27 Bead Array.

5

ΔβN-averageC.

6

p values (Welch's t-test) of <0.05 are underlined.