Table 3. p-AMPK status and patient mortality in strata of p-MAPK3/1 status (upper rows) and p-MAPK3/1 status and patient mortality in strata of p-AMPK status (lower rows).

	Colorectal cancer-specific mortality			Overall mortality
	No. of deaths/cases	Univariate HR (95% CI)	Multivariate stage-matched HR (95% CI)	No. of deaths/cases	Univariate HR (95% CI)	Multivariate stage-matched HR (95% CI)
p-MAPK3/1 (−)
p-AMPK (−)	59/227	1 (referent)	1 (referent)	84/227	1 (referent)	1 (referent)
p-AMPK (+)	72/242	1.14 (0.81–1.61)	1.22 (0.85–1.75)	106/242	1.20 (0.90–1.60)	1.31 (0.98–1.76)
p-MAPK3/1 (+)
p-AMPK (−)	23/57	1 (referent)	1 (referent)	32/57	1 (referent)	1 (referent)
p-AMPK (+)	27/145	0.39 (0.23–0.69)	0.42 (0.24–0.74)	62/145	0.64 (0.42–0.98)	0.65 (0.42–1.01)
p-AMPK (−)
p-MAPK3/1 (−)	59/227	1 (referent)	1 (referent)	84/227	1 (referent)	1 (referent)
p-MAPK3/1 (+)	23/57	1.75 (1.08–2.82)	1.94 (1.17–3.24)	32/57	1.67 (1.12–2.50)	1.88 (1.23–2.86)
p-AMPK (+)
p-MAPK3/1 (−)	72/242	1 (referent)	1 (referent)	106/242	1 (referent)	1 (referent)
p-MAPK3/1 (+)	27/145	0.55 (0.36–0.85)	0.55 (0.35–0.86)	62/145	0.84 (0.62–1.14)	0.80 (0.58–1.10)
Pinteraction (p-AMPK and p-MAPK3/1)	0.0014	0.0017		0.016	0.0026

Abbreviations: BMI=body mass index; CI=confidence interval; HR=hazard ratio; p-AMPK=phosphorylated AMP-activated protein kinase; p-MAPK3/1=phosphorylated mitogen-activated protein kinase. The multivariate, stage-matched (stratified) Cox model included p-AMPK variable stratified by p-MAPK3/1 status (or p-MAPK3/1 variable stratified by p-AMPK status), sex, age, year of diagnosis, BMI, tumour location, tumour grade, tumour border, CIMP, MSI, LINE-1 methylation, BRAF, KRAS, PIK3CA, TP53 and FASN. A backward stepwise elimination with a threshold of P=0.20 was used to select variables in the final model. Stage adjustment (I, IIA, IIB, IIIA, IIIB, IIIC, IV, unknown) was done using the ‘strata’ option in the SAS ‘proc phreg’ command.