Table 3.

Ordinal logistic regression analysis to assess the association of tumor PDCD1LG2 (PD-L2) expression (predictor) with histologic lymphocytic reaction (outcome)

Univariable OR (95% CI)Multivariable OR (95% CI)a
Model for Crohn-like lymphoid reaction as an ordinal outcome variable (n = 680)
 Fraction of PDCD1LG2-expressing tumor cells (quartile)bQuartile 11 (reference)1 (reference)
Quartile 20.78 (0.49–1.24)0.79 (0.48–1.30)
Quartile 30.61 (0.39–0.95)0.58 (0.36–0.93)
Quartile 40.38 (0.22–0.64)0.38 (0.22–0.67)
Ptrendc0.00020.0003
Model for peritumoral lymphocytic reaction as an ordinal outcome variable (n = 811)
 Fraction of PDCD1LG2-expressing tumor cells (quartile)bQuartile 11 (reference)1 (reference)
Quartile 21.18 (0.77–1.82)1.20 (0.78–1.85)
Quartile 31.06 (0.71–1.58)1.09 (0.73–1.64)
Quartile 40.97 (0.63–1.50)1.01 (0.65–1.57)
Ptrendc0.810.98
Model for intratumoral periglandular reaction as an ordinal outcome variable (n = 813)
 Fraction of PDCD1LG2-expressing tumor cells (quartile)bQuartile 11 (reference)1 (reference)
Quartile 21.28 (0.81–2.04)1.32 (0.83–2.11)
Quartile 30.95 (0.61–1.46)0.99 (0.64–1.53)
Quartile 40.72 (0.45–1.14)0.75 (0.47–1.20)
Ptrendc0.100.16
Model for TILs as an ordinal outcome variable (n = 812)
 Fraction of PDCD1LG2-expressing tumor cells (quartile)bQuartile 11 (reference)1 (reference)
Quartile 21.19 (1.78–1.82)1.34 (0.84–2.13)
Quartile 30.92 (0.61–1.39)0.92 (0.58–1.44)
Quartile 40.67 (0.42–1.07)0.81 (0.49–1.35)
Ptrendc0.070.23
  • aThe multivariable ordinal logistic regression analysis model initially included age, sex, year of diagnosis, family history of colorectal carcinoma in any parent or sibling, tumor location, MSI, CpG island methylator phenotype, KRAS, BRAF, and PIK3CA mutations, and LINE-1 methylation level. A backward elimination with a threshold of P = 0.05 was used to select variables in the final models. Variables remaining in the final multivariable model for Crohn-like lymphoid reaction were shown in Supplementary Table S3.

  • bTumors were categorized into quartiles according to the percentage of PDCD1LG2–expressing carcinoma cells (quartile 1, 0%–20%; quartile 2, 21%–50%; quartile 3, 51%–80%; quartile 4, 81%–100%).

  • cPtrend value was calculated by the linear trend across the ordinal quartile categories of tumor PDCD1LG2 expression (1–4; as a predictor variable) in the ordinal logistic regression model for each histologic pattern of lymphocytic reaction (negative/low, intermediate, and high; as an ordinal outcome variable). Because we assessed four primary outcome variables, we adjusted two-sided α level to 0.01 (≈0.05/4) by simple Bonferroni correction.