Skip to main content

Table 5 Association between immune cell ratios and methylation-based CRP scores and lung cancer-specific mortality among lung cancer cases, CLUE I/II cohort

From: Methylation-derived inflammatory measures and lung cancer risk and survival

 

All lung cancersa

HR (95% CI)

Non-small cell lung cancerb

HR (95% CI)

mdNLRc

1.28 (1.09, 1.50)

1.47 (1.20, 1.81)

 Time to diagnosis ≤ 10 years

1.34 (1.01, 1.76)

1.73 (1.19, 2.51)

 Time to diagnosis > 10 years

1.20 (0.98, 1.48)

1.39 (1.05, 1.85)

CD4/CD8 ratioc

1.02 (0.76, 1.36)

1.07 (0.78, 1.48)

 Time to diagnosis ≤ 10 years

1.28 (0.79, 2.07)

1.29 (0.70, 2.38)

 Time to diagnosis > 10 years

0.96 (0.65, 1.41)

1.03 (0.66, 1.62)

B cell/lymphocyte ratioc

0.97 (0.73, 1.30)

1.06 (0.74, 1.51)

 Time to diagnosis ≤ 10 years

0.87 (0.50, 1.50)

0.99 (0.52, 1.89)

 Time to diagnosis > 10 years

1.11 (0.75, 1.63)

1.18 (0.75, 1.85)

T cell/lymphocyte ratioc

1.01 (0.78, 1.31)

0.95 (0.69, 1.31)

 Time to diagnosis ≤ 10 years

1.01 (0.62, 1.64)

0.94 (0.53, 1.68)

 Time to diagnosis > 10 years

1.05 (0.69, 1.60)

0.91 (0.54, 1.52)

Monocyte/Lymphocyte Ratioc

1.16 (0.87, 1.55)

1.21 (0.85, 1.72)

 Time to diagnosis ≤ 10 years

1.45 (0.87, 2.43)

1.52 (0.80, 2.89)

 Time to diagnosis > 10 years

1.25 (0.80, 1.96)

1.54 (0.84, 2.84)

(Neutrophil + monocyte)/lymphocyte ratioc

1.29 (1.00, 1.67)

1.48 (1.04, 2.11)

 Time to diagnosis ≤ 10 years

1.36 (0.87, 2.13)

1.76 (0.95, 3.24)

 Time to diagnosis > 10 years

1.22 (0.86, 1.74)

1.41 (0.87, 2.29)

Eosinophil/lymphocyte ratioc

1.01 (0.76, 1.35)

0.86 (0.60, 1.23)

 Time to diagnosis ≤ 10 years

1.55 (0.93, 2.59)

1.40 (0.74, 2.67)

 Time to diagnosis > 10 years

0.98 (0.67, 1.44)

0.77 (0.49, 1.21)

CD4 naïve/lymphocyte ratioc

0.92 (0.67, 1.27)

0.95 (0.65, 1.40)

 Time to diagnosis ≤ 10 years

0.92 (0.53, 1.59)

0.73 (0.35, 1.53)

 Time to diagnosis > 10 years

0.91 (0.60, 1.38)

0.99 (0.61, 1.60)

B cell/CD8 ratioc

1.03 (0.82, 1.29)

1.07 (0.83, 1.38)

 Time to diagnosis ≤ 10 years

1.01 (0.69, 1.49)

1.04 (0.64, 1.69)

 Time to diagnosis > 10 years

1.05 (0.71, 1.55)

1.20 (0.74, 1.95)

CD8/treg ratioc

0.92 (0.67, 1.27)

0.92 (0.63, 1.35)

 Time to diagnosis ≤ 10 years

0.73 (0.42, 1.26)

0.63 (0.30, 1.32)

 Time to diagnosis > 10 years

1.03 (0.66, 1.62)

1.09 (0.63, 1.88)

Treg > 0 versus treg = 0c

0.96 (0.72, 1.28)

0.91 (0.64, 1.30)

 Time to diagnosis ≤ 10 years

1.27 (0.76, 2.13)

1.37 (0.70, 2.69)

 Time to diagnosis > 10 years

0.85 (0.58, 1.25)

0.75 (0.45, 1.26)

B cell naïve/B cell memory Ratioc

1.09 (0.84, 1.41)

1.23 (0.89, 1.70)

 Time to diagnosis ≤ 10 years

1.31 (0.86, 1.99)

1.66 (0.74, 3.71)

 Time to diagnosis > 10 years

1.03 (0.75, 1.42)

1.19 (0.73, 1.93)

CD4 naïve/CD4 memory ratioc

0.97 (0.70, 1.34)

1.03 (0.70, 1.52)

 Time to diagnosis ≤ 10 years

0.91 (0.53, 1.57)

0.71 (0.32, 1.59)

 Time to diagnosis > 10 years

1.00 (0.64, 1.57)

1.17 (0.70, 1.96)

CD8 naïve/CD8 memory ratioc

0.96 (0.70, 1.32)

1.10 (0.77, 1.57)

 Time to diagnosis ≤ 10 years

1.09 (0.63, 1.88)

1.19 (0.59, 2.42)

 Time to diagnosis > 10 years

0.92 (0.61, 1.40)

1.05 (0.67, 1.65)

CRP Score 1cd

0.92 (0.67, 1.26)

0.88 (0.60, 1.30)

 Time to diagnosis ≤ 10 years

1.00 (0.57, 1.75)

1.22 (0.67, 2.22)

 Time to diagnosis > 10 years

1.04 (0.67, 1.63)

0.82 (0.46, 1.46)

CRP Score 2cd

0.86 (0.65, 1.13)

0.98 (0.69, 1.41)

 Time to diagnosis ≤ 10 years

0.76 (0.47, 1.23)

1.11 (0.61, 2.03)

 Time to diagnosis > 10 years

1.10 (0.73, 1.66)

0.93 (0.55, 1.56)

CRP Score 3cd

1.05 (0.76, 1.47)

1.07 (0.73, 1.59)

 Time to diagnosis ≤ 10 years

1.01 (0.56, 1.81)

1.01 (0.46, 2.22)

 Time to diagnosis > 10 years

1.16 (0.74, 1.83)

1.22 (0.69, 2.16)

  1. Bold HR and CI values indicate statistical significance. Underline HR and CI values indicate borderline statistical significance after multiple comparison adjustment
  2. a205 cases (3 cases with person-year = 0 or > 25 years were removed from the analytical dataset) Model adjusted for age at blood draw, sex, smoking status, BMI, surrogate variables for batch effects, and a pack-year-based smoking methylation score. The results for Inflammation Scores additional adjust for cell proportions. BMI was removed from model when stratified by BMI. Group person-year: all lung cancer cases = 421.3; cases with time to diagnosis ≤ 10 years = 104.3; cases with time to diagnosis > 10 years = 316.9; cases with BMI < 25 kg/m2 = 184.3; cases with BMI ≥ 25 kg/m2 = 236.9
  3. b149 cases (1 case with person-year =  >25 years were removed from the analytical dataset) Model adjusted for age at blood draw, sex, smoking status, BMI, surrogate variables for batch effects, and methylation-predicted pack-years smoked. The results for Inflammation Scores additional adjust for cell proportions. BMI was removed from model when stratified by BMI. Group person-year for all non-small cell lung cancer (NSCLC) cases = 337.6; NSCLC cases with time to diagnosis ≤ 10 years = 84.4; NSCLC cases with time to diagnosis > 10 years = 253.2; NSCLC cases with BMI < 25 kg/m2 = 141.4; NSCLC cases with BMI ≥ 25 kg/m2 = 196.2
  4. cHR results reported per 1 unit of SD increase among all cases (mdNLR SD: 1.86; CD4/CD8 ratio SD: 2.14; BL ratio SD: 0.0534; TL ratio SD: 0.0844; ML ratio SD: 0.125; NM/L ratio SD: 1.38; EL ratio SD: 0.079; CD4nv/L ratio SD: 0.0920; B/CD8 ratio SD: 2.21; CD8/Treg ratio SD: 112; Bnv/Bmem ratio SD: 81.3; CD4nv/CD4mem ratio SD: 0.335; CD8nv/CD8mem ratio SD: 1.64; CpG Score 1 SD: 0.979; CpG Score 2 SD: 0.945; CpG Score 3 SD: 1.02) and HR results reported for Treg > 0 versus Treg = 0 among all cases; Bonferroni-adjusted CI reported for all except mdNLR and CRP Scores 1–3 (a prior hypotheses)
  5. dCpG Scores 1, 2, and 3 are built using 54 CpG sites, the top 10 highly cell-specific CpG sites, and the 10 modestly cell-specific CpG sites, respectively