Table 3. Tumor LINE-1 hypomethylation and patient survival according to colorectal cancer location and MSI status.
No. of cases | Colorectal cancer-specific mortality | Overall mortality | |||||
---|---|---|---|---|---|---|---|
No. of events | Univariable HR (95% CI) | Multivariable HR (95% CI)a | No. of events | Univariable HR (95% CI) | Multivariable HR (95% CI)a | ||
MSI-low/MSS proximal colon cancer | |||||||
LINE-1 hypomethylation (20% decrease as a unit) | 440 | 153 | 1.77 (1.26-2.50) | 1.44 (1.04-2.01) | 259 | 1.41 (1.07-1.84) | 1.27 (0.97-1.66) |
Pb | 0.001 | 0.030 | 0.014 | 0.08 | |||
MSI-high proximal colon cancer | |||||||
LINE-1 hypomethylation (20% decrease as a unit) | 181 | 23 | 4.51 (1.78-11.4) | 6.14 (2.27-16.6) | 85 | 1.62 (0.96-2.74) | 2.30 (1.30-4.06) |
Pb | 0.002 | 0.0003 | 0.07 | 0.004 | |||
MSI-low/MSS distal colon cancer | |||||||
LINE-1 hypomethylation (20% decrease as a unit) | 388 | 108 | 1.21 (0.84-1.76) | 1.13 (0.76-1.66) | 203 | 0.97 (0.73-1.28) | 1.06 (0.80-1.41) |
Pb | 0.31 | 0.55 | 0.82 | 0.69 | |||
MSI-high distal colon cancer | |||||||
LINE-1 hypomethylation (20% decrease as a unit) | 21 | 3 | 3.05 (0.74-12.6) | 2.76 (0.75-10.1) | 8 | 2.38 (0.89-6.36) | 2.00 (0.87-4.60) |
Pb | 0.12 | 0.13 | 0.08 | 0.10 | |||
Rectal cancer | |||||||
LINE-1 hypomethylation (20% decrease as a unit) | 287 | 95 | 0.92 (0.60-1.40) | 0.87 (0.57-1.34) | 162 | 0.79 (0.57-1.09) | 0.72 (0.52-1.00) |
Pb | 0.69 | 0.52 | 0.15 | 0.052 |
CI, confidence interval; HR, hazard ratio; LINE-1, long interspersed nucleotide element-1; MSI, microsatellite instability; MSS, microsatellite stable.
The multivariable Cox regression model initially included sex, age, year of diagnosis, family history of colorectal cancer in parent or sibling, disease stage, tumor differentiation, CpG island methylator phenotype, and KRAS, BRAF, and PIK3CA mutations. A backward elimination with a threshold of P = 0.05 was used to select variables in the final models.
P value was calculated by the Wald test (two-sided).