Different oncological features of colorectal cancer codon-specific KRAS mutations: Not codon 13 but codon 12 have prognostic value

Table 3 Univariable and Cox regression analyses of KRAS mutations for determination of recurrence-related factors

	Recurrence			Multivariable Cox regression analysis2
	Absent1 (n = 1998)	Present1 (n = 205)	P value	HR	95%CI		P value
					Lower	Upper
Age (yr)			0.716
< 65	933 (46.7)	93 (45.4)		-	-	-	-
≥ 65	1065 (53.3)	112 (54.6)		-	-	-
Sex			0.616
Male	1143 (57.2)	121 (59.0)		-	-	-	-
Female	855 (42.8)	84 (41.0)		-	-	-
BMI			0.094
< 25 kg/m2	1266 (63.4)	142 (69.3)		-	-	-	-
≥ 25 kg/m2	732 (36.6)	63 (30.7)		-	-	-
ASA score			0.980
1-2	1802 (90.2)	185 (90.2)		-	-	-	-
3-4	196 (9.8)	20 (9.8)		-	-	-
Cancer location (1)3			0.860
Right-sided	577 (28.9)	58 (28.3)		-	-	-	-
Left-sided	1421 (71.1)	147 (71.7)		-	-	-
Cancer location (2)4
Colon	1376 (68.9)	127 (62.0)	0.043	1.000
Rectum	622 (31.1)	78 (38.0)		1.053	0.718	1.545	0.791
Preoperative CEA			< 0.001
< 5.0 ng/mL	1607 (80.4)	140 (68.3)		1.000
≥ 5.0 ng/mL	391 (19.6)	65 (31.7)		1.158	0.849	1.579	0.354
Diverting stoma			< 0.001
No	1568 (78.5)	138 (67.3)		1.000
Yes	430 (21.5)	67 (32.7)		1.874	1.260	2.787	0.002
T stage			< 0.001
T0-2	659 (33.0)	17 (8.3)		1.000
T3-4	1339 (67.0)	188 (91.7)		2.620	1.479	4.641	0.001
N stage			< 0.001
N0	1230 (61.6)	56 (27.3)		1.000
N1-2	768 (38.4)	149 (72.7)		2.001	1.399	2.861	< 0.001
MSI status			0.037
MSS	1680 (84.1)	186 (90.7)		0.855	0.342	2.138	0.738
MSI-low	143 (7.2)	10 (4.9)		1.284	0.643	2.566	0.479
MSI-high	175 (8.8)	9 (4.4)		1.000
Tumor size (cm)	4.3 ± 2.4	4.9 ± 2.1	< 0.001	0.997	0.927	1.074	0.944
Lymphatic invasion			< 0.001
No	1493 (74.7)	113 (55.1)		1.000
Yes	505 (25.3)	92 (44.9)		1.324	0.977	1.793	0.070
Vascular invasion			< 0.001
No	1615 (80.8)	119 (58.0)		1.000
Yes	383 (19.2)	86 (42.0)		1.578	1.164	2.139	0.003
Perineural invasion			< 0.001
No	1211 (60.6)	58 (28.3)		1.000
Yes	787 (39.4)	147 (71.7)		1.684	1.194	2.376	0.003
Harvested LN	45.3 ± 21.2	44.9 ± 21.4	0.705	-	-	-	-
Metastatic LN	1.2 ± 2.6	3.3 ± 4.5	< 0.001	1.028	0.995	1.061	0.095
KRAS Codon 12
Wild-type	1459 (73.0)	133 (64.9)	0.013	1.000
Mutation	539 (27.0)	72 (35.1)		1.399	1.034	1.894	0.030
KRAS Codon 13
Wild-type	1809 (90.5)	193 (94.1)	0.088	1.000
Mutation	189 (9.5)	12 (5.9)		0.637	0.350	1.160	0.140
KRAS Codon 61
Wild-type	1975 (98.8)	200 (97.6)	0.176	1.000
Mutation	23 (1.2)	5 (2.4)		1.950	0.790	4.812	0.147

¹Results are reported as mean ± SD or as number (percent).

²No values indicated variables do not match the covariance input criterion (P < 0.1 in univariable analysis).

³Right-sided: From the cecum to distal 2/3 transverse colon; Left-sided: From the splenic flexure to rectum.

⁴Rectum: Below the pelvic inlet (an imaginary line drawn from the sacral promontory to the pubic symphysis).

KRAS: Kirsten rat sarcoma viral oncogene homolog; HR: Hazard ratio; CI: Confidence interval; BMI: Body mass index; ASA: American Society of Anesthesiologists; CEA: Carcinoembryonic antigen; MSI: Microsatellite instability; MSS: Microsatellite stable; LN: Lymph node.