Prognostic value of KRAS and BRAF mutations in curatively resected colorectal cancer

doi:10.3748/wjg.v21.i4.1275

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastroenterol. Jan 28, 2015; 21(4): 1275-1283
Published online Jan 28, 2015. doi: 10.3748/wjg.v21.i4.1275

Table 1 Patient characteristics according to BRAF or KRAS status n (%)

Characteristics	KRAS status			BRAF status
Characteristics	Wild-type n = 500	Mutant n = 312	P value	Wild-type n = 771	Mutant n = 40	P value
Age (yr)			0.11			0.40
mean ± SD	63.5 ± 10.3	64.7 ± 10.3	0.11	63.9 ± 10.3	65.4 ± 11.6	0.40
Gender			0.02			0.006
Male	308 (62)	166 (53)		459 (60)	15 (38)
Female	192 (38)	146 (47)		312 (40)	25 (63)
Tumor location			0.37			< 0.001
Proximal	134 (27)	98 (31)		201 (26)	31 (78)
Distal	213 (43)	125 (40)		332 (43)	5 (13)
Rectum	153 (31)	89 (29)		238 (31)	4 (10)
Histological grade			0.24			< 0.001
Well/moderate	472 (94)	288 (92)		728 (94)	31 (78)
Poor/mucinous	28 (6)	24 (8)		43 (6)	9 (23)
T stage			0.12			0.89
1	52 (10)	31 (10)		79 (10)	4 (10)
2	106 (21)	46 (15)		145 (19)	7 (18)
3	286 (57)	200 (64)		462 (60)	23 (58)
4	56 (11)	35 (11)		85 (11)	6 (15)
LN metastasis			0.18			0.96
Yes	180 (36)	127 (41)		292 (38)	15 (38)
No	320 (64)	185 (59)		479 (62)	25 (63)
TNM stage			0.09			0.92
I	125 (25)	58 (19)		173 (22)	10 (25)
II	195 (39)	127 (41)		306 (40)	15 (38)
III	180 (36)	127 (41)		292 (38)	15 (38)
Adjuvant chemotherapy			0.44			0.57
Yes	217 (43)	144 (46)		344 (45)	16 (40)
No	283 (57)	168 (54)		427 (55)	24 (60)
MSI status			0.33			< 0.001
MSS/MSI-L	455 (91)	290 (93)		728 (94)	16 (40)
MSI-H	45 (9)	22 (7)		43 (6)	24 (60)

SD: Standard deviation; LN: Lymph node; TNM: Tumor-Node-Metastasis; MSI: Microsatellite instability; MSS: Microsatellite stable; MSI-L: Microsatellite instability-low; MSI-H: Microsatellite instability-high.

Table 2 Univariate prognostic analysis of disease-free survival and overall survival

Characteristics	Disease-free survival		Overall survival
Characteristics	HR	95%CI	HR	95%CI
Age (yr)
< 65	1	Reference	1	Reference
≥ 65	1.73	1.35-2.28	2.21	1.64-2.98
Gender
Female	1	Reference	1	Reference
Male	1.57	1.20-2.06	1.57	1.16-2.13
Tumor location
Proximal	1	Reference	1	Reference
Distal	0.92	0.67-1.25	0.9	0.64-1.26
Rectum	1.17	0.85-1.62	0.97	0.67-1.40
Histological grade
Well/moderate	1	Reference	1	Reference
Poor/mucinous	1.53	0.97-2.42	1.43	0.84-2.42
AJCC stage
I	1	Reference	1	Reference
II	2.6	1.61-4.19	2.26	1.36-3.75
III	4.68	2.95-7.42	3.49	2.14-5.70
Adjuvant chemotherapy
No	1	Reference	1	Reference
Yes	1.24	0.96-1.60	1.29	1.10-1.51
MSI
MSS/MSI-L	1	Reference	1	Reference
MSI-H	0.71	0.42-1.20	0.92	0.54-1.59
KRAS
Wild-type	1	Reference	1	Reference
Mutant	1.35	1.04-1.74	1.44	1.08-1.92
BRAF
Wild-type	1	Reference	1	Reference
Mutant	1.38	0.82-2.32	1.57	0.90-2.76

HR: Hazard ratio; CI: Confidence interval; MSI: Microsatellite instability; MSS: Microsatellite stable; MSI-L: Microsatellite instability-low; MSI-H: Microsatellite instability-high.

Table 3 Prognostic effects of microsatellite instability, KRAS, and BRAF status in Cox proportional models

	Disease-free survival¹		Overall survival¹
	HR (95%CI)	P value	HR (95%CI)	P value
MSI
MSS/MSI-L	1 (reference)	0.14	1 (reference)	0.53
MSI-H	0.64 (0.35-1.16)		0.81 (0.42-1.56)
KRAS
Wild-type	1 (reference)	0.03	1 (reference)	0.01
Mutant	1.35 (1.03-1.75)		1.46 (1.09-1.97)
BRAF
Wild-type	1 (reference)	0.01	1 (reference)	0.02
Mutant	2.20 (1.19-4.06)		2.30 (1.15-4.71)

¹Covariates include age (< 65 or ≥ 65), gender, AJCC stage (I/II/III), adjuvant chemotherapy (Yes/No), and MSI, KRAS, and BRAF status. CI: Confidence interval; MSI: Microsatellite instability; MSS: Microsatellite stable; MSI-L: Microsatellite instability-low; MSI-H: Microsatellite instability-high.

Table 4 Prognostic Effects of KRAS and BRAF mutations according to microsatellite instability status

	KRAS		BRAF
	HR (95%CI)	P value	HR (95%CI)	P value
DFS¹
MSS/MSI-L	1.37 (1.05-1.80)	0.95	2.06 (0.96-4.43)	0.91
MSI-H	1.34 (0.34-5.24)		2.46 (0.49-12.4)
OS¹
MSS/MSI-L	1.49 (1.10-2.02)	0.70	2.74 (1.19-6.30)	0.44
MSI-H	1.39 (0.33-5.78)		1.18 (0.23-6.02)

¹Covariates include age, gender, AJCC stage (I-II/III), adjuvant chemotherapy, and KRAS and BRAF status. HR: Hazard ratio; CI: Confidence interval; DFS: Disease-free survival; OS: Overall survival; MSI: Microsatellite instability; MSS: Microsatellite stable; MSI-L: Microsatellite instability-low; MSI-H: Microsatellite instability-high.

Citation: Kadowaki S, Kakuta M, Takahashi S, Takahashi A, Arai Y, Nishimura Y, Yatsuoka T, Ooki A, Yamaguchi K, Matsuo K, Muro K, Akagi K. Prognostic value of KRAS and BRAF mutations in curatively resected colorectal cancer. World J Gastroenterol 2015; 21(4): 1275-1283
URL: https://www.wjgnet.com/1007-9327/full/v21/i4/1275.htm
DOI: https://dx.doi.org/10.3748/wjg.v21.i4.1275