Table 5.
Inverse Probability Weighting (IPW)-Adjusted Logistic Regression Analysis to Assess the Associations of Fusobacterium nucleatum (Predictor) with T Cell Density (Outcome) in Strata of Exome-wide Tumor Mutational Burden
| N = 424 | Univariable OR (95% CI)* | Multivariable OR (95% CI)*,† |
|---|---|---|
| Model for stromal CD3+ cell density‡ (as an outcome variable) | ||
| Exome-wide tumor mutational burden-low | ||
| Amount of F. nucleatum DNA | ||
| Negative | 1 (referent) | 1 (referent) |
| Low | 1.08 (0.32–3.64) | 1.07 (0.30–3.76) |
| High | 0.48 (0.11–2.07) | 0.43 (0.09–2.09) |
| Exome-wide tumor mutational burden-high | ||
| Amount of F. nucleatum DNA | ||
| Negative | 1 (referent) | 1 (referent) |
| Low | 0.42 (0.15–1.18) | 0.47 (0.17–1.33) |
| High | 0.68 (0.26–1.80) | 0.75 (0.28–2.06) |
| Pinteraction§ | 0.68 | 0.77 |
| Model for stromal CD3+CD4+CD45RO+ cell density‡ (as an outcome variable) | ||
| Exome-wide tumor mutational burden-low | ||
| Amount of F. nucleatum DNA | ||
| Negative | 1 (referent) | 1 (referent) |
| Low | 1.15 (0.34–3.87) | 1.15 (0.34–3.97) |
| High | 0.51 (0.12–2.20) | 0.50 (0.12–2.19) |
| Exome-wide tumor mutational burden-high | ||
| Amount of F. nucleatum DNA | ||
| Negative | 1 (referent) | 1 (referent) |
| Low | 0.41 (0.14–1.14) | 0.43 (0.15–1.22) |
| High | 0.65 (0.25–1.71) | 0.78 (0.29–2.15) |
| Pinteraction§ | 0.71 | 0.82 |
IPW was applied to reduce a bias due to the availability of tumor tissue after cancer diagnosis (see “Statistical Analysis” subsection for details).
The multivariable logistic regression model initially included age, sex, year of diagnosis, family history of colorectal cancer, tumor location, microsatellite instability, CpG island methylator phenotype, long-interspersed nucleotide element-1 methylation level, and KRAS, BRAF, and PIK3CA mutation status. A backward elimination with a threshold P of 0.20 was used to select variables for the final model.
To avoid violation of the proportional odds assumption, the densities of T cells were dichotomized at the median value of each subset.
Pinteraction (two-sided) was calculated using the Wald test for the cross product of F. nucleatum DNA amount (negative, low, and high, as an ordinal predictor variable) and exome-wide tumor mutational burden [high (Q3–4) vs. low (Q1–2)] in the IPW-adjusted logistic regression model.
Abbreviations: CI, confidence interval; IPW, inverse probability weighting; OR, odds ratio.