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

Table 2 Univariable analysis¹ of each codon-specific KRAS mutation

	KRAS overall2			KRAS Codon 12			KRAS Codon 13			KRAS Codon 61
	WT (%)	MT (%)	P value	WT (%)	MT (%)	P value	WT (%)	MT (%)	P value	WT (%)	MT (%)	P value
Age			0.418			0.734			0.698			0.246
< 65 yr	644 (62.8)	382 (37.2)		745 (72.6)	281 (27.4)		936 (91.1)	91 (8.9)		1016 (99.0)	10 (1.0)
≥ 65 yr	719 (61.1)	458 (38.9)		847 (72.0)	330 (28.0)		1067 (90.7)	110 (9.3)		1160 (98.5)	18 (1.5)
Sex			< 0.001			< 0.001			0.006			0.238
Male	851 (67.3)	413 (32.7)		961 (76.0)	303 (24.0)		1167 (92.3)	97 (7.7)		1251 (99.0)	13 (1.0)
Female	512 (54.5)	427 (45.5)		631 (67.2)	308 (32.8)		836 (88.9)	104 (11.1)		924 (98.4)	15 (1.6)
BMI			0.098			0.347			0.485			0.104
< 25 kg/m2	853 (60.6)	555 (39.4)		1008 (71.6)	400 (28.4)		1275 (90.6)	133 (9.4)		1386 (98.4)	22 (1.6)
≥ 25 kg/m2	510 (64.2)	285 (35.8)		584 (73.5)	211 (26.5)		727 (91.4)	68 (8.6)		789 (99.2)	6 (0.8)
ASA score			0.010			0.002			0.942			0.347
1-2	1212 (61.0)	775 (39.0)		1417 (71.3)	570 (28.7)		1806 (90.9)	181 (9.1)		1963 (98.8)	24 (1.2)
3-4	151 (69.9)	65 (30.1)		175 (81.0)	41 (19.0)		196 (90.7)	20 (9.3)		212 (98.1)	4 (1.9)
Cancer location (1)3			< 0.001			0.002			< 0.001			0.219
Right-sided	329 (51.8)	306 (48.2)		429 (67.6)	206 (32.4)		546 (86.0)	89 (14.0)		624 (98.3)	11 (1.7)
Left-sided	1034 (65.9)	534 (34.1)		1163 (74.2)	405 (25.8)		1456 (92.9)	112 (7.1)		1552 (98.9)	17 (1.1)
Cancer location (2)4			0.092			0.405			0.117			0.966
Colon	912 (60.7)	591 (39.3)		1078 (71.7)	425 (28.3)		1356 (90.2)	147 (9.8)		1484 (98.7)	19 (1.3)
Rectum	451 (64.4)	249 (35.6)		514 (73.4)	186 (26.6)		646 (92.3)	54 (7.7)		691 (98.7)	9 (1.3)
Preoperative CEA			< 0.001			< 0.001			0.037			0.301
< 5.0 ng/mL	1131 (64.7)	616 (35.3)		1299 (74.4)	448 (25.6)		1599 (91.5)	148 (8.5)		1727 (98.9)	20 (1.1)
≥ 5.0 ng/mL	232 (50.9)	224 (49.1)		293 (64.3)	163 (35.7)		403 (88.4)	53 (11.6)		448 (98.2)	8 (1.8)
Diverting stoma			0.001			0.071			0.029			0.131
No	1024 (60.0)	682 (40.0)		1217 (71.3)	489 (28.7)		1538 (90.2)	168 (9.8)		1681 (98.5)	25 (1.5)
Yes	339 (68.2)	158 (31.8)		375 (75.5)	122 (24.5)		464 (93.4)	33 (6.6)		494 (99.4)	3 (0.6)
T stage			0.008			0.003			0.488			0.139
T0-2	446 (66.0)	230 (34.0)		517 (76.5)	159 (23.5)		610 (90.2)	66 (9.8)		671 (99.3)	5 (0.7)
T3-4	917 (60.1)	610 (39.9)		1075 (70.4)	452 (29.6)		1392 (91.2)	135 (8.8)		1504 (98.5)	23 (1.5)
N stage			0.012			0.046			0.617			0.094
N0	824 (64.1)	462 (35.9)		950 (73.9)	336 (26.1)		1172 (91.1)	114 (8.9)		1274 (99.1)	12 (0.9)
N1-2	539 (58.8)	378 (41.2)		642 (70.0)	275 (30.0)		830 (90.5)	87 (9.5)		901 (98.3)	16 (1.7)
MSI status			0.003			0.001			0.458			0.973
MSS	1138 (61.0)	728 (39.0)		1327 (71.1)	539 (28.9)		1701 (91.2)	165 (8.8)		1842 (98.7)	24 (1.3)
MSI-low	90 (58.8)	63 (41.2)		110 (71.9)	43 (28.1)		135 (88.2)	18 (11.8)		151 (98.7)	2 (1.3)
MSI-high	135 (73.4)	49 (26.6)		155 (84.2)	29 (15.8)		166 (90.2)	18 (9.8)		182 (98.9)	2 (1.1)
Tumor size (cm)	4.3 ± 2.4	4.6 ± 2.3	0.005	4.3 ± 2.5	4.6 ± 2.1	0.001	4.4 ± 2.3	4.6 ± 2.7	0.837	4.4 ± 2.4	4.5 ± 2.1	0.708
Lymphatic invasion			0.005			0.099			0.080			0.302
No	1022 (63.6)	584 (36.4)		1176 (73.2)	430 (26.8)		1470 (91.5)	136 (8.5)		1589 (98.9)	18 (1.1)
Yes	341 (57.1)	256 (42.9)		416 (69.7)	181 (30.3)		532 (89.1)	65 (10.9)		587 (98.3)	10 (1.7)
Vascular invasion			0.090			0.047			0.614			0.061
No	1057 (61.0)	677 (39.0)		1236 (71.3)	498 (28.7)		1573 (90.7)	161 (9.3)		1716 (99.0)	18 (1.0)
Yes	306 (65.2)	163 (34.8)		356 (75.9)	113 (24.1)		429 (91.5)	40 (8.5)		459 (97.9)	10 (2.1)
Perineural invasion			0.003			0.027			0.387			0.048
No	819 (64.5)	450 (35.5)		940 (74.1)	329 (25.9)		1159 (91.3)	110 (8.7)		1258 (99.1)	11 (0.9)
Yes	544 (58.2)	390 (41.8)		652 (69.8)	282 (30.2)		843 (90.3)	91 (9.7)		917 (98.2)	17 (1.8)
Harvested LN	44.5 ± 20.6	46.5 ± 22.1	0.040	45.0 ± 21.1	45.9 ± 21.6	0.500	45.0 ± 20.9	47.9 ± 24.1	0.079	45.2 ± 21.3	47.7 ± 16.6	0.208
Metastatic LN	1.4 ± 3.1	1.3 ± 2.6	0.420	1.4 ± 3.1	1.3 ± 2.4	0.406	1.4 ± 2.9	1.4 ± 3.1	0.832	1.4 ± 2.9	1.4 ± 1.9	0.149

¹The continuous variables were compared using either independent t-test or Mann-Whitney U test; the categorical variables were compared using Chi-square or Fisher’s exact test.

²Kirsten rat sarcoma viral oncogene homolog overall indicates at least one mutation within codon 12, 13, or 61.

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; WT: Wild-type; MT: Mutation; BMI: Body mass index; ASA: American Society of Anesthesiologists; CEA: Carcinoembryonic antigen; MSI: Microsatellite instability; MSS: Microsatellite stable; LN: Lymph node.