CIMP (≥ 2 loci) CIMP (≥ 3 loci) CIMP (≥ 4 loci) CIMP (= 5 loci) Tissue Characteristics Category + - P + - P + - P + - P NSC Total   12 27   10 41   7 73   3 11   LC     3     9     7     6 4     Gender Male (n=84) 69 15   66 18   43 41   18 66     Female (n=66) 54 12 1.00 43 23 0.10 34 32 1.00 18 48 0.41   Age < 60y(n=19) 11 8   9 10   9 10   3 16     ≥60y (n=131) 112 19 0.008** 100 31 0.01* 68 63 0.81 33 98 0.54   Histological type Adenocarcinoma (n=52) 40 12   33 19   19 33   14 38     Squamous cell (n=65) 55 10   50 15   35 30   14 51     Large cell (n=33) 28 5 0.50 26 7 0.20 23 10 0.01* 8 25 0.79   Tumor size < 3 cm (n=71) 56 15   52 19   34 37   14 57     ≥3 cm (n=79) 67 12 0.40 57 22 1.09 43 36 0.51 22 57 0.33   Stage I/II (n =107) 87 20   75 32   53 54   25 82     III/IV (n=43) 36 7 0.82 34 9 0.36 24 19 0.59 11 32 0.83   Smoking history Never (n=9) 8 1   7 2   5 4   3 6     Light (< 20 pky, n=15) 15 0   13 2   11 4   6 9     Heavy (≥20 pky, n=124) 98 26   87 37   60 64   27 97     Unknown (n=2) 2 0 0.18 2 0 0.54 1 1 0.26 0 2 0.32   Tumor location Left lobe (n=65) 55 10   48 17   36 29   13 52     Right lobe (n=85) 68 17 0.53 61 24 0.85 41 44 0.41 23 62 0.34 TFS Total   1 14   1 14   0 14   0 14   LT       1     1     2     2     Gender Male (n=83) 1 84   1 84   0 85   0 85     Female (n=59) 0 59 1.00 0 59 1.00 0 59 1.00 0 59 1.00   Age <60y(n=21) 0 21   0 21   0 21   0 21     ≥60y (n=121) 1 120 1.00 1 120 1.00 0 121 1.00 0 121 1.00

*P<0.05; ** P<0.01; a CpG island methylator phenotype.

Table 3: The association analyses of clinical characteristics with gene co-methylation status (CIMPa).