Epigenomic diversity of colorectal cancer indicated by LINE-1 methylation in a database of 869 tumors

Table 2 Multivariate linear regression analysis to predict LINE-1 methylation level in 869 colorectal cancers

Variables in the final model	Adjusted β coefficient (change in LINE-1 methylation level by a given variable)	95% confidence limits	P value (partial F-test)
CIMP status			< 0.0001
CIMP-high (vs. CIMP-0)	4.79	2.69, 6.89	< 0.0001 (T test)
CIMP-low (vs. CIMP-0)	1.17	-0.18, 2.52	0.090 (T test)
Signet ring cell component (for 10% increase)	1.15	0.53, 1.77	0.0003
Rectal location (vs. colon)	2.22	0.68, 3.75	0.0046
Family history of colorectal cancer (present vs. absent)	-1.92	-3.36, -0.48	0.0089
Disease stage (for one unit increase in ordinal scale, I-IV)	-0.83	-1.50, -0.16	0.016
CDKN1A (p21) loss (vs. expression)	-2.06	-3.75, -0.37	0.017
Crohn's-like reaction [for one unit increase in ordinal scale 1 (absent)-4 (strong)]	1.26	-0.20, 2.31	0.020
High tumor grade (vs. low grade)	-2.47	-5.00, 0.07	0.056
Male (vs. female)	1.03	-0.24, 2.29	0.11
Body mass index (BMI, for an increase of 5 kg/m²)	0.50	-0.18, 1.18	0.15

The multivariate linear regression model initially included the variables listed in the table, age, smoking, mucinous component, peritumoral lymphocytic reaction, tumor infiltrating lymphocytes, CTNNB1 score, MSI status, mutations in BRAF, KRAS and PIK3CA, and expression status of TP53, CDKN1A (p21), PTGS2 (cyclooxygenase-2), and FASN. A backward elimination with a threshold of p = 0.20 was performed to select variables in the final model. The adjusted β coefficient represents a change (increase or decrease) in LINE-1 methylation level by a given variable, assuming that all other variables remain constant. R-square of the multivariate model was only 0.084, indicating that 92% of variability in LINE-1 methylation levels remained unexplained by this model. A p value for significance is adjusted to p = 0.0021 by Bonferroni correction for multiple hypothesis testing.
CIMP, CpG island methylator phenotype; MSI, microsatellite instability.

ISSN: 1476-4598