Predictive and Prognostic Implications of Mutation Profiling and Microsatellite Instability Status in Patients with Metastatic Colorectal Carcinoma

Table 4

Univariate and multivariate analyses of OS and PFS for 461 metastatic colorectal cancer patients.

Parameter	Variable	OS univariate	Analysis	OS multivariate	Analysis	PFS univariate	Analysis	PFS multivariate	Analysis
		HR (95% CI)	value	HR (95% CI)	value	HR (95% CI)	value	HR (95% CI)	value
Gender	Male versus female	0.998 (0.773–1.287)	0.985			1.026 (0.795–1.325)	0.841
Age, years	<65 versus ≥65	1.310 (1.013–1.694)	0.039	1.330 (0.998–1.772)	0.052	1.067 (0.827–1.376)	0.619
Tumor location	Left/right colon versus rectum	1.013 (0.884–1.162)	0.849			1.089 (0.950–1.249)	0.220
Primary tumor size, cm	<5 versus ≥5	1.077 (0.783–1.480)	0.650			1.311 (0.955–1.800)	0.094
Differentiation	Well/moderate versus poor	1.031 (0.790–1.345)	0.823			1.322 (1.016–1.721)	0.038	0.395 (0.145–1.075)	0.069
Histological type	Papillary/tubular adenocarcinoma versus mucinous/signet ring cell	1.142 (0.829–1.575)	0.416			1.280 (0.929–1.764)	0.131
Depth of invasion	T1 + T2 versus T3 + T4	0.952 (0.728–1.244)	0.717			1.184 (0.912–1.536)	0.205
Nodal stage	N0 + N1 versus N2a + N2b	1.162 (0.980–1.378)	0.084			1.245 (1.053–1.474)	0.011	1.119 (0.920–1.361)	0.260
Metastatic site	Brain + lung versus liver + others	1.540 (1.174–2.020)	0.002	1.536 (1.130–2.088)	0.006	1.728 (1.321–2.260)	<0.001	1.481 (1.094–2.006)	0.011
COX-2 expression	Negative versus positive	1.046 (0.779–1.406)	0.765			0.945 (0.704–1.270)	0.709
Initial CEA (ng/mL)	<20 versus ≥20	3.103 (1.913–5.034)	<0.001	2.257 (1.366–3.730)	0.001	2.659 (1.641–4.310)	<0.001	1.838 (1.113–3.036)	0.017
MSI	MSI-H versus MSI-L/MSS	0.782 (0.493–1.238)	0.294			0.688 (0.435–1.089)	0.110
C-MET expression	Negative/weak versus moderate/strong	1.690 (1.275–2.240)	<0.001	1.429 (1.052–1.940)	0.022	1.495 (1.129–1.979)	0.005	1.351 (0.993–1.839)	0.055
KRAS mutation	Yes versus no	2.112 (1.620–2.754)	<0.001	1.826 (1.361–2.450)	<0.001	2.050 (1.574–2.671)	<0.001	2.082 (1.545–2.805)	<0.001
BRAF mutation	Yes versus no	8.615 (5.537–9.045)	<0.001	4.798 (2.989–7.700)	<0.001	4.458 (2.935–6.771)	<0.001	3.864 (2.375–6.287)	<0.001
NRAS mutation	Yes versus no	0.620 (0.230–1.668)	0.344			0.462 (0.472–1.242)	0.126
Anti-EGFR therapy	Yes versus no	0.599 (0.401–0.894)	0.012	0.742 (0.463–1.189)	0.215	0.694 (0.465–1.036)	0.074
Bevacizumab therapy	Yes versus no	0.713 (0.529–0.963)	0.027	0.663 (0.469–0.937)	0.020	0.758 (0.562–1.022)	0.069	0.682 (0.484–0.961)	0.029
Surgery	Yes versus no	0.702 (0.532–0.927)	0.013	0.758 (0.531–1.082)	0.127	0.712 (0.539–0.941)	0.017	0.745 (0.525–1.057)	0.099

OS = overall survival; PFS = progression-free survival; HR = hazard ratio; CI = confidence interval; COX-2 = cyclooxygenase-2; C-MET = mesenchymal-epithelial transition factor; CEA = carcinoembryonic antigen; MSI = microsatellite instability; MSI-H = MSI-high; MSI-L = MSI-low; MSS = microsatellite stability.