Differential effects of the KRAS gene on recurrence in right- vs left-sided colorectal liver metastases undergoing radiofrequency ablation

doi:10.4240/wjgs.v17.i8.108418

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World Journal of Gastrointestinal Surgery

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Retrospective Cohort Study

World J Gastrointest Surg. Aug 27, 2025; 17(8): 108418
Published online Aug 27, 2025. doi: 10.4240/wjgs.v17.i8.108418

Table 1 Demographic and clinicopathologic characteristics, n (%)

Characteristics	No. of patients (n = 164)	*KRAS*
Characteristics	No. of patients (n = 164)	Wild (n = 89)	Mutation (n = 75)	P value
Age (year), mean	58.0 ± 9.8	57.0 ± 9.5	59.1 ± 10.0	0.167
≤ 60	90 (54.9)	51 (56.7)	39 (43.3)	0.497
> 60	74 (45.1)	38 (51.4)	36 (48.6)
Sex				0.794
Male	98 (59.8)	54 (55.1)	44 (44.9)
Female	66 (40.2)	35 (53.0)	31 (47.0)
Primary tumor site				0.017
Right colon	27 (16.5)	9 (33.3)	18 (66.7)
Left colon	137 (83.5)	80 (58.4)	57 (41.6)
Primary tumor invasion				0.203
T1-2	11 (6.7)	8 (72.7)	3 (27.3)
T3-4	153 (93.3)	81 (52.9)	72 (47.1)
Nodal status of primary tumor				0.561
Positive	128 (78.0)	71 (55.5)	57 (44.5)
Negative	36 (22.0)	18 (50.0)	18 (50.0)
Time of CLM				0.504
Synchronous	85 (51.8)	44 (51.8)	41 (48.2)
Heterochronous	79 (48.2)	45 (57.0)	34 (43.0)
Extrahepatic metastases				0.139
Yes	75 (45.7)	36 (48.0)	39 (52.0)
No	89 (54.3)	53 (59.6)	36 (40.4)
Tumor size (cm)
Median diameter, cm (quartile)	2.2 (1.7-2.9)	2.0 (1.7-2.7)	2.2 (1.6-3.3)	0.236
≤ 3	123 (75.0)	71 (57.8)	52 (42.2)	0.124
> 3	41 (25.0)	18 (43.9)	23 (56.1)
DFI (months)				0.485
< 12	137 (83.5)	76 (55.5)	61 (44.5)
≥ 12	27 (16.5)	13 (48.1)	14 (51.9)
CEA level (ng/mL)				0.914
≤ 30	135 (82.3)	73 (54.1)	62 (45.9)
> 30	29 (17.7)	16 (55.2)	13 (44.8)
CRS				0.313
0-2	77 (47.0)	45 (58.4)	32 (41.6)
3-5	87 (53.0)	44 (50.6)	43 (49.4)
Liver metastases resection pre-RFA				0.485
Yes	66 (40.2)	38 (57.6)	28 (42.4)
No	98 (59.8)	51 (52.0)	47 (48.0)
Preoperative chemotherapy				0.221
Yes	148 (90.2)	78 (52.7)	70 (47.3)
No	16 (9.8)	11 (68.8)	5 (31.2)
Ablative margin (mm)				0.156
< 5	17 (10.4)	7 (41.2)	10 (58.8)
5-10	101 (61.6)	52 (51.5)	49 (48.5)
> 10	46 (28.0)	30 (65.2)	16 (34.8)

DFI: Disease-free interval from primary resection to the diagnosis of liver metastasis; CRS: Node-positive primary tumor, DFI < 12 months, more than one liver tumor, size of largest tumor > 3 cm, carcinoembryonic antigen level > 30 ng/mL (mg/L); RFA: Radiofrequency ablation; CLM: Colorectal liver metastases; CEA: Carcinoembryonic antigen.

Table 2 Recurrence after colorectal liver metastases underwent radiofrequency ablation, n (%)

Characteristic	All patients (n = 164)	Right colon			Left colon
Characteristic	All patients (n = 164)	Wild (n = 9)	Mutation (n = 18)	P value	Wild (n = 80)	Mutation (n = 57)	P value
Intrahepatic recurrence	101 (61.6)	5 (55.6)	10 (55.6)	1.000	42 (52.5)	44 (77.2)	0.003
Extrahepatic recurrence	88 (53.7)	5 (55.6)	7 (38.9)	0.448	43 (53.7)	33 (57.9)	0.630
Number				1.000			0.460
Single	79 (89.8)	4 (80.0)	6 (85.7)		40 (93.0)	29 (87.9)
Multiple	9 (10.2)	1 (20.0)	1 (14.3)		3 (7.0)	4 (12.1)
Site of single extrahepatic recurrence
Lung	38 (48.1)	2 (50.0)	2 (33.3)	0.582	20 (50.0)	14 (48.3)	1.000
Bone	11 (13.9)	0	2 (33.3)	0.538	5 (10.0)	4 (13.8)	1.000
Peritoneal	8 (10.1)	0	0	-	4 (8.0)	4 (13.8)	0.719
Ovary	4 (5.1)	1 (25.0)	0	0.333	2 (4.0)	1 (3.4)	1.000
Adrenal	2 (2.5)	0	0	-	0	2 (6.9)	0.171
Lymph node	15 (19.0)	1 (25.0)	2 (33.3)	1.000	8 (16.0)	4 (13.8)	0.761
Other	1 (1.3)	0	0	-	1 (2.0)	0	1.000
RFS¹	10 (0-57)	11 (1-35)	14 (1-45)	0.944	11 (0-57)	9 (0-44)	0.012
Intrahepatic RFS¹	19 (0-86)	13 (1-35)	15 (1-49)	0.950	25 (0-86)	15 (0-63)	0.007
Extrahepatic RFS¹	23 (0-95)	22 (2-35)	37 (1-47)	0.515	27 (0-57)	22 (0-95)	0.467

¹Data are medians, with ranges in parentheses. Unless indicated otherwise, data indicates the number of patients, with percentages in parentheses.

RFS: Recurrence-free survival.

Table 3 Univariable and multivariable analyses of prognostic factors for recurrence-free survival for colorectal liver metastases

Prognostic factor	Univariable analysis		Multivariable analysis
Prognostic factor	HR (95%CI)	P value	HR (95%CI)	P value
Age (year)	0.890 (0.622-1.273)	0.523
Tumor size > 3 cm	1.070 (0.715-1.602)	0.743
Sex	1.112 (0.776-1.593)	0.563
Right colon	1.072 (0.657-1.748)	0.781
Pathological differentiation/poorly	0.766 (0.430-1.364)	0.366
KRAS mutation	1.507 (1.058-2.148)	0.023	1.526 (1.056-2.207)	0.025
T stage	0.910 (0.461-1.796)	0.786
Lymph node metastasis	1.674 (1.064-2.635)	0.026	1.602 (1.008-2.545)	0.046
Synchronous liver metastasis	0.824 (0.580–1.169)	0.278
No. of liver metastases	1.414 (0.992-2.014)	0.055	1.241 (0.857-1.797)	0.253
Liver metastasis resection pre-RFA	1.414 (0.990-2.019)	0.057	1.418 (0.988-2.034)	0.058
Extrahepatic metastases	1.066 (0.745-1.524)	0.727
CRS	1.238 (0.869-1.762)	0.236
CEA	0.893 (0.563-1.417)	0.631
DFI	1.043 (0.645-1.686)	0.863
Preoperative chemotherapy	1.111 (0.611-2.017)	0.731

DFI: Disease-free interval from primary resection to the diagnosis of liver metastasis; CRS: Clinical risk score, including node-positive primary tumor, DFI < 12 months, more than one liver tumor, size of largest tumor > 3 cm, carcinoembryonic antigen level > 30 ng/mL (mg/L); RFA: Radiofrequency ablation; CEA: Carcinoembryonic antigen.

Table 4 Univariable and multivariable analyses of prognostic factors for overall survival for colorectal liver metastases

Prognostic factor	Univariable analysis		Multivariable analysis
Prognostic factor	HR (95%CI)	P value	HR (95%CI)	P value
Age (year)	1.057 (0.707-1.579)	0.787
Tumor size > 3 cm	1.598 (1.037-2.464)	0.034	1.829 (1.124-2.972)	0.015
Sex	0.898 (0.599-1.347)	0.604
Right colon	2.098 (1.258-3.498)	0.005	2.234 (1.298-3.845)	0.004
Pathological differentiation/poorly	1.465 (0.813-2.638)	0.203
KRAS mutation	1.681 (1.123-2.515)	0.012	1.325 (0.865-2.031)	0.196
T stage	1.338 (0.583-3.070)	0.492
Lymph node metastases	1.317 (0.787-2.201)	0.294
Synchronous liver metastasis	1.267 (0.846-1.898)	0.252
No. of liver metastases	1.708 (1.124-2.594)	0.012	1.469 (0.839-2.570)	0.178
Liver metastasis resection pre-RFA	0.803 (0.526-1.226)	0.310
Extrahepatic metastases	1.849 (1.229-2.782)	0.003	1.700 (1.113-2.598)	0.014
CRS	1.690 (1.115-2.561)	0.013	1.174 (0.658-2.095)	0.587
CEA	1.069 (0.636-1.797)	0.802
DFI	1.279 (0.755-2.167)	0.360
Margin	1.216 (0.843-1.755)	0.295
Preoperative chemotherapy	1.623 (0.751-3.508)	0.218

Citation: Jiang BB, Wang JC, Yan K, Zhang ZY, Wang S, Wu W, Yang W. Differential effects of the KRAS gene on recurrence in right- vs left-sided colorectal liver metastases undergoing radiofrequency ablation. World J Gastrointest Surg 2025; 17(8): 108418
URL: https://www.wjgnet.com/1948-9366/full/v17/i8/108418.htm
DOI: https://dx.doi.org/10.4240/wjgs.v17.i8.108418