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 |
Probe ID for the Infinium HumanMethylation27 Bead Array.
ΔβN-averageC.
p values (Welch's t-test) of <0.05 are underlined.
Probe ID for the Infinium HumanMethylation27 Bead Array.
ΔβN-averageC.
p values (Welch's t-test) of <0.05 are underlined.