KRAS genotypes predict metachronous colorectal cancer distant metastases after radical resections

doi:10.16139/j.1007-9610.2021.01.014

Abstract

Abstract:

Objective To explore the relationship between KRAS genotype and metachronous distant metastases in patients with colorectal cancer after radical resections. Methods Patients were analyzed retrospectively with metachronous distant metastases group and non-metastases group. PCR and pyrosequencing were used to detect the genotype of KRAS. Clinicopathological data and the KRAS genotype were analyzed to find the predictor for metachronous distant metastases. Results A total of 186 patients were enrolled in this study: 93 cases in metachronous distant metastases group and 93 cases in non-metastases group. KRAS gene mutation type was significantly associated with preoperative CEA(P=0.015) and metachronous distant metastases (P<0.001). The multivariate analyses showed that female (OR=0.426, P=0.020), tumor located at rectum (OR=0.408, P=0.040) and the type of mucinous adenocarcinoma (OR=0.230, P=0.010) were independent protective factors for metachronous distant metastases. Pathological N₂ stage (OR=4.191, P=0.003), KRAS mutation type of p.G12V (OR=10.568, P=0.001) and p.G13D (OR=12.657, P<0.001) were 2 independent risk factors for metachronous distant metastases. The model of multivariate prediction was gotten based on 5 factors and was significantly better than prediction of single factor with TNM stage or KRAS genotype (multivariate model, AUC=0.767; TNM stage, AUC=0.569; KRAS genotype, AUC=0.628; P<0.001). Conclusions p.G12V and p.G13D mutation type of KRAS gene were independent risk factors for metachronous distant metastases. Multivariate prediction model was constructed for prediction of metachronous colorectal cancer distance metastases.

Key words: Colorectal cancer, Metachronous distant metastases, KRAS

CLC Number:

LIN Songbin, FENG Qingyang, XU Jianmin. KRAS genotypes predict metachronous colorectal cancer distant metastases after radical resections[J]. Journal of Surgery Concepts & Practice, 2021, 26(01): 66-71.

Figures/Tables 6

References 15

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项目	总体	转移组	无转移组
总计	186	93	93
野生型	117 (62.9)	49 (52.7)	68 (73.1)
突变型	69 (37.1)	44 (47.3)	25 (26.9)
c.35G>A, p.G12D	23 (12.4)	9 (9.7)	14 (15.1)
c.35G>T, p.G12V	16 (8.6)	12 (12.9)	4 (4.3)
c.34G>T, p.G12C	2 (1.1)	0	2 (2.2)
c.35G>C, p.G12A	1 (0.5)	1 (1.1)	0
c.34G>A, p.G12S	1 (0.5)	1 (1.1)	0
c.34G>C, p.G12R	1 (0.5)	0	1 (1.1)
c.38G>A, p.G13D	25 (13.4)	21 (22.6)	4 (4.3)

项目	总体（n=186）	野生型（n=117）	c.35G>A,p.G12D （n=23）	c.35G>T,p.G12V （n=16）	c.38G>A,p.G13D （n=25）	其他突变类型（n=5）	检验值	P值
性别							4.080	0.259
男	110 (59.1)	75 (64.1)	11 (47.8)	7 (43.8)	14 (56.0)	3 (60.0)
女	76 (40.9)	42 (35.9)	12 (52.2)	9 (56.2)	11 (44.0)	2 (40.0)
年龄(岁)							3.436	0.345
≤60	86 (46.2)	58 (49.6)	11 (47.8)	4 (25.0)	12 (48.0)	1 (20.0)
>60	100 (53.8)	59 (50.4)	12 (52.2)	12 (75.0)	13 (52.0)	4 (80.0)
术前CEA(μg/L)							10.330	0.015^a)
<5	113 (60.8)	78 (66.7)	14 (60.9)	4 (25.0)	15 (60.0)	2 (40.0)
≥5	73 (39.2)	39 (33.3)	9 (39.1)	12 (75.0)	10 (40.0)	3 (60.0)
原发灶部位							4.347	0.637^b)
右半结肠	54 (29.0)	34 (29.1)	8 (34.8)	4 (25.0)	6 (24.0)	2 (40.0)
左半结肠	49 (26.3)	35 (29.9)	3 (13.0)	3 (18.8)	8 (32.0)	0
直肠	83 (44.6)	48 (41.0)	12 (52.2)	9 (56.2)	11 (44.0)	3 (60.0)
组织学类型							1.655	0.643^b)
腺癌	155 (83.3)	99 (84.6)	18 (78.3)	15 (93.8)	21 (84.0)	2 (40.0)
黏液腺癌	31 (16.7)	18 (15.4)	5 (21.7)	1 (6.2)	4 (16.0)	3 (60.0)
分化程度							3.145	0.375
高/中分化	109 (58.6)	66 (56.4)	12 (52.2)	11 (68.8)	18 (72.0)	2 (40.0)
低/未分化	77 (41.4)	51 (43.6)	11 (47.8)	5 (31.2)	7 (28.0)	3 (60.0)
pT分期							5.588	0.465^b)
1~2	25 (13.4)	18 (15.4)	1 (4.3)	3 (18.8)	2 (8.0)	1 (20.0)
3	65 (34.9)	36 (30.8)	10 (43.5)	4 (25.0)	12 (48.0)	3 (60.0)
4	96 (51.6)	63 (53.8)	12 (52.2)	9 (56.2)	11 (44.0)	1 (20.0)
pN分期							11.302	0.073^a)b)
0	77 (41.4)	43 (36.8)	12 (52.2)	12 (75.0)	9 (36.0)	1 (20.0)
1	66 (35.5)	41 (35.0)	6 (26.1)	3 (18.8)	12 (48.0)	4 (80.0)
2	43 (23.1)	33 (28.2)	5 (21.7)	1 (6.2)	4 (16.0)	0
异时性远处转移							19.728	<0.001^a)
无	93 (50.0)	68 (58.1)	14 (60.9)	4 (25.0)	4 (16.0)	3 (60.0)
有	93 (50.0)	49 (41.9)	9 (39.1)	12 (75.0)	21 (84.0)	2 (40.0)

项目	单因素分析			多因素分析
项目	OR	95%CI	P值	OR	95%CI	P值
性别
男	1	-	-	1	-	-
女	0.640	0.355~1.152	0.137	0.426	0.207~0.876	0.020^a)
年龄（岁）
≤60	1	-	-	1	-	-
>60	0.841	0.472~1.498	0.556	0.693	0.336~1.427	0.319
术前CEA（μg/L）
<5	1	-	-	1	-	-
≥5	1.145	0.635~2.063	0.652	0.899	0.444~1.820	0.767
原发灶部位
右半结肠	1	-	-	1	-	-
左半结肠	0.656	0.301~1.429	0.289	0.500	0.200~1.248	0.138
直肠	0.658	0.330~1.312	0.234	0.408	0.173~0.961	0.040^a)
组织学类型
腺癌	1	-	-	1	-	-
黏液腺癌	0.490	0.220~1.090	0.080	0.230	0.075~0.709	0.010^a)
分化程度
高/中分化	1	-	-	1	-	-
低/未分化	0.957	0.534~1.715	0.882	1.377	0.613~3.093	0.439
pT分期
1~2	1	-	-	1	-	-
3	1.645	0.645~4.197	0.297	1.304	0.416~4.086	0.649
4	1.564	0.639~3.826	0.327	1.182	0.397~3.524	0.764
pN分期
0	1	-	-	1	-	-
1	1.190	0.615~2.303	0.605	1.365	0.605~3.083	0.454
2	2.134	0.993~4.585	0.052	4.191	1.643~10.691	0.003^a)
原发灶术后静脉化疗
FOLFOX	1	-	-	1	-	-
XELOX	1.962	0.740~5.198	0.175	1.806	0.590~5.522	0.300
未化疗	0.864	0.338~2.210	0.761	0.580	0.181~1.856	0.359
KRAS基因型
野生型	1	-	-	1	-	-
c.35G>A, p.G12D	0.892	0.358~2.226	0.807	1.258	0.454~3.485	0.658
c.35G>T, p.G12V	4.163	1.267~13.681	0.019^a)	10.568	2.568~43.499	0.001^a)
c.38G>A, p.G13D	7.286	2.352~22.567	0.001^a)	12.657	3.607~44.411	<0.001^a)
其他突变	0.925	0.149~5.747	0.933	2.927	0.381~22.493	0.302