Novel tumor marker index combining carcinoembryonic antigen and carbohydrate antigen 19-9: New prognostic factor for metastatic colorectal cancer

doi:10.4251/wjgo.v17.i5.104341

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World Journal of Gastrointestinal Oncology

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1948-5204

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

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World J Gastrointest Oncol. May 15, 2025; 17(5): 104341
Published online May 15, 2025. doi: 10.4251/wjgo.v17.i5.104341

Table 1 Baseline demographic and clinical characteristics of patients according to tumor marker index groups, n (%)

	Total (n = 305)	TMI-low (n = 151)	TMI-high (n = 154)	P value
Age, mean ± SD	64.5 ± 12.4	64.1 ± 12.8	64.9 ± 12.0	0.56^a
≤ 65 years	150 (49.2)	76 (50.3)	74 (48.1)	0.69^b
> 65 years	155 (50.8)	75 (49.7)	80 (51.9)	0.69^b
Sex
Female	113 (37.0)	58 (38.4)	55 (35.7)	0.63^b
Male	192 (63.0)	93 (61.6)	99 (64.3)	0.63^b
ECOG-PS
0	108 (35.4)	54 (35.8)	54 (35.1)	0.18^c
1	156 (51.1)	83 (55)	73 (47.4)
2	36 (11.8)	12 (7.9)	24 (15.6)
3	5 (1.6)	2 (1.3)	3 (1.9)
BMI
≤ 25 kg/m²	201 (65.9)	109 (72.2)	92 (59.7)	0.02^b
> 25 kg/m²	104 (34.1)	42 (27.8)	62 (40.3)	0.02^b
Smoking history
No	172 (56.4)	81 (53.6)	91 (59.1)	0.34^b
Yes	133 (43.6)	70 (46.4)	63 (40.9)	0.34^b
Alcohol using
No	280 (91.8)	138 (91.4)	142 (92.2)	0.79^b
Yes	25 (8.2)	13 (8.6)	12 (7.8)	0.79^b
DM
No	244 (80.0)	123 (81.5)	121 (78.6)	0.53^b
Yes	61 (20.0)	28 (18.5)	33 (21.4)	0.53^b
HT
No	199 (65.2)	102 (67.5)	97 (63)	0.40^b
Yes	106 (34.8)	49 (32.5)	57 (37)	0.40^b
CAD
No	265 (86.9)	132 (87.4)	133 (86.4)	0.78^b
Yes	40 (13.1)	19 (12.6)	21 (13.6)	0.78^b
Disease status
De-novo metastatic	209 (68.5)	96 (63.6)	113 (73.4)	0.06^b
Recurrent metastatic	96 (31.5)	55 (36.4)	41 (26.6)	0.06^b
History of adjuvant CT
No	206 (67.5)	94 (62.3)	112 (72.7)	0.05^b
Yes	99 (32.5)	57 (37.7)	42 (27.3)	0.05^b
Liver metastasis
No	92 (31.2)	56 (37.1)	36 (23.4)	0.01^b
Yes	213 (69.8)	95 (62.9)	118 (76.6)	0.01^b
Lung metastasis
No	201 (65.9)	104 (68.9)	97 (63)	0.28^b
Yes	104 (34.1)	47 (31.1)	57 (37)	0.28^b
Bone metastasis
No	281 (92.1)	142 (94)	139 (90.3)	0.22^b
Yes	24 (7.9)	9 (6)	15 (9.7)	0.22^b
Peritoneal metastasis
No	233 (76.4)	106 (70.2)	127 (82.5)	0.01^b
Yes	72 (23.6)	45 (29.8)	27 (17.5)	0.01^b
Number of metastatic site
1	157 (51.5)	80 (53)	77 (50)	0.35^b
2	91 (29.8)	48 (31.8)	43 (27.9)
3	38 (12.5)	17 (11.3)	21 (13.6)
4 or more	19 (6.2)	6 (4)	13 (8.4)
Isolated liver metastasis
No	207 (67.9)	106 (70.2)	101 (65.6)	0.39^b
Yes	98 (32.1)	45 (29.8)	53 (34.4)	0.39^b
History of metastasectomy
No	242 (79.3)	110 (72.8)	132 (85.7)	0.006^b
Yes	63 (20.7)	41 (27.2)	22 (14.3)	0.006^b
Tumor location
Right side colon cancer	65 (21.3)	27 (17.9)	38 (24.7)	0.29^b
Left side colon cancer	140 (45.9)	70 (46.4)	70 (45.5)
Rectum cancer	100 (32.8)	54 (35.8)	46 (29.9)
KRAS
Wild	182 (59.7)	98 (64.9)	84 (54.5)	0.02^b
Mutant	93 (30.5)	35 (23.2)	58 (37.7)
Unknown	30 (9.8)	18 (11.9)	12 (7.8)
NRAS
Wild	236 (77.4)	114 (75.5)	122 (79.2)	0.26^b
Mutant	20 (6.6)	8 (5.3)	12 (7.8)
Unknown	49 (16.1)	29 (19.2)	20 (13)
BRAF
Wild	241 (79.0)	118 (78.1)	123 (79.9)	0.79^b
Mutant	10 (3.3)	6 (4)	4 (2.6)
Unknown	54 (17.7)	27 (17.9)	27 (17.5)
MSI status
Microsatellite stable	183 (60.0)	85 (56.3)	98 (63.6)	0.42^b
MSI-high	11 (3.6)	6 (4)	5 (3.2)
Unknown	111 (36.4)	60 (39.7)	51 (33.1)
Metastatic line(s) of CT
1	120 (40.0)	61 (40.9)	59 (39.1)	0.66^b
2	87 (29.0)	46 (30.9)	41 (27.2)
3	41 (13.7)	17 (11.4)	24 (15.9)
4 and more	52 (17.3)	25 (16.8)	27 (17.9)
Using immunotherapy
No	302 (99.0)	150 (99.3)	152 (98.7)	0.99^c
Yes	3 (1.0)	1 (0.7)	2 (1.3)	0.99^c
GPS
0	134 (43.9)	78 (51.7)	56 (36.4)	0.03^b
1	132 (43.3)	57 (37.7)	75 (48.7)
2	39 (12.8)	16 (10.6)	23 (14.9)
NLR, mean ± SD	3.45 ± 2.55	3.15 ± 1.98	3.76 ± 2.98	0.04^c

^aIndependent t test, P < 0.05 statistically significant.

^bPearson χ² test, P < 0.05 statistically significant.

^cFisher’s exact test, P < 0.05 statistically significant.

TMI: Tumor marker index; ECOG-PS: Eastern Cooperative Oncology Group Performance Status; BMI: Body mass index; DM: Diabetes mellitus; HT: Hypertension; CAD: Coronary artery disease; CT: Chemotherapy; MSI: Microsatellite instability; GPS: Glasgow prognostic score; NLR: Neutrophil-to-lymphocyte ratio.

Table 2 Patients’ treatment responses according to the tumor marker index high and tumor marker index low groups, n (%)

	Total (n = 305)	TMI-low (n = 151)	TMI-high (n = 154)	P value
Best response				0.19
CR	20 (6.6)	14 (9.2)	6 (3.9)
PR	116 (38)	57 (37.7)	59 (38.3)
SD	102 (33.4)	46 (30.5)	56 (36.4)
PD	40 (13.1)	17 (11.3)	23 (14.9)
Missing/unknown	27 (8.9)	17 (11.3)	10 (6.5)
Objective response rate (CR + PR)	136 (44.6)	71 (47.0)	65 (42.2)	0.40
Disease control rate (CR + PR + SD)	238 (78)	117 (77.5)	121 (78.6)	0.82

TMI: Tumor marker index; CR: Complete response; PR: Partial remission; SD: Stable disease; PD: Progressive disease.

Table 3 Univariate and multivariate analyses for progression-free survival

Variable	Univariate analyses	P value	Multivariate analyses	P value
Variable	Median PFS (95%CI), month	P value	HR (95%CI)	P value
Age
≤ 65 years	15.9 (13.5-18.3)	0.29
> 65 years	13.9 (12.2-15.7)	0.29
Gender
Female	14.3 (11.1-17.5)	0.77
Male	14.5 (12.8-16.3)	0.77
ECOG-PS
0	14.7 (11.5-17.9)	0.18
1	15.9 (14.0-17.7)
2	10.1 (7.8-12.3)
3	25.1 (0.3-49.9)
BMI
≤ 25 kg/m²	13.9 (13.0-14.8)	0.08
> 25 kg/m²	19.9 (14.4-25.4)	0.08
Smoking history
No	14.5 (12.4-16.5)	0.69
Yes	14.4 (11.0-17.8)	0.69
Disease status
De novo metastatic	13.2 (12.5-14.6)	0.002^a	Ref	0.71
Recurrent metastatic	23.7 (16.5-30.9)	0.002^a	0.90 (0.53-1.52)
History of adjuvant CT
No	13.5 (12.3-14.6)	0.004^a	Ref	0.30
Yes	21.7 (16.0-27.4)	0.004^a	0.79 (0.44-1.22)
Liver metastasis
No	17.6 (8.7-26.5)	0.05
Yes	14.3 (13.1-15.5)	0.05
Lung metastasis
No	14.5 (12.5-16.5)	0.30
Yes	14.4 (11.9-16.9)	0.30
Bone metastasis
No	14.4 (12.8-16.0)	0.73
Yes	19.4 (11.1-27.7)	0.73
Peritoneal metastasis
No	14.4 (12.8-15,9)	0.28
Yes	17.5 (11.0-23.9)	0.28
Number of metastatic site
1	15.0 (13.0-17.0)	0.004^a	Ref
2	15.8 (12.1-19.4)		1.92 (1.34-2.75)	< 0.001^a
3	10.3 (8.4-12.1)		2.20 (1.44-3.36)	< 0.001^a
4 and more	14.2 (3.4-24.9)		1.39 (0.93-2.09)	0.10
Isolated liver metastasis
No	14.5 (12.6-16.6)	0.68
Yes	14.3 (11.7-17.0)	0.68
History of metastasectomy
No	14.0 (11.9-16.0)	0.01^a	Ref	0.06
Yes	16.9 (12.7-21.1)	0.01^a	0.71 (0.50-1.01)
Tumor location
Right side colon cancer	13.4 (11.4-15.4)	0.54
Left side colon cancer	17.3 (13.3-21.3)
Rectum cancer	13.5 (11.6-15.4)
KRAS
Wild	13.9 (12.6-15.2)	0.003^a	Ref
Mutant	14.6 (12.3-16.8)		0.91 (0.66-1.23)	0.52
Unknown	28.7 (5.8-51.6)		0.51 (0.21-1.21)	0.13
NRAS
Wild	13.9 (12.8-15.0)	0.001^a	Ref
Mutant	17.5 (0.00-47.5)		0.67 (0.36-1.26)	0.22
Unknown	25.1 (17.1-33.1)		0.77 (0.39-1.54)	0.47
BRAF
Wild	14.4 (12.8-15.9)	0.01^a	Ref
Mutant	8.4 (0.0-17.0)		1.57 (0.81-3.04)	0.18
Unknown	20.4 (11.6-29.2)		1.21 (0.71-2.07)	0.48
MSI status
Microsatellite stable	14.3 (12.8-15.9)	0.30
MSI-high	- (-)
Unknown	16.0 (13.4-18.5)
GPS
0	18.3 (15.5-21.0)	0.07
1	13.9 (13.0-14.9)
2	12.6 (9.1-16.1)
NLR
< 2.76	16.5 (12.9-20.1)	0.17
≥ 2.76	13.9 (12.6-15.2)	0.17
TMI
< 1.39	16.0 (13.4-18.4)	0.84
≥ 1.39	14.0 (12.7-15.2)	0.84

^aP < 0.05.

PFS: Progression-free survival; HR: Hazard ratio; CI: Confidence interval; ECOG-PS: Eastern Cooperative Oncology Group Performance Status; BMI: Body mass index; CT: Chemotherapy; MSI: Microsatellite instability; GPS: Glasgow prognostic score; NLR: Neutrophil-to-lymphocyte ratio; TMI: Tumor marker index.

Table 4 Univariate and multivariate analyses for overall survival

Variable	Univariate analyses	P value	Multivariate analyses	P value
Variable	Median OS (95%CI), month	P value	HR (95%CI)	P value
Age
≤ 65 years	42.4 (33.7-51.0)	0.09
> 65 years	32.0 (22.2-41.7)	0.09
Gender
Female	41.9 (31.9-52.0)	0.17
Male	36.5 (27.8-45.1)	0.17
ECOG-PS
0	47.5 (32.2-62.7)	< 0.001^a	Ref
1	36.7 (28.4-45.0)		1.31 (0.88-1.97)	0.18
2	18.2 (13.7-22.7)		3.52 (2.00-6.22)	< 0.001^a
3	19.6 (16.2-23.0)		1.56 (0.53-4.51)	0.41
BMI
≤ 25 kg/m²	32.4 (24.5-40.3)	0.09
> 25 kg/m²	47.1 (37.0-57.0)	0.09
Smoking history
No	42.4 (33.8-51.1)	0.13
Yes	30.1 (20.8-39.4)	0.13
Disease status
De novo metastatic	38.7 (30.7-46.6)	0.24
Recurrent metastatic	36.5 (19.8-53.2)	0.24
History of adjuvant CT
No	32.3 (23.1-41.6)	0.06
Yes	43.5 (30.0-57.0)	0.06
Liver metastasis
No	35.7 (28.3-43.0)	0.78
Yes	39.9 (29.1-50.5)	0.78
Lung metastasis
No	40.2 (32.8-47.4)	0.42
Yes	32.3 (23.2-41.5)	0.42
Bone metastasis
No	40.0 (32.7-47.3)	0.26
Yes	31.9 (18.5-45.2)	0.26
Peritoneal metastasis
No	38.6 (30.0-47.3)	0.83
Yes	38.3 (29.2-47.4)	0.83
Number of metastatic site
1	40.1 (32.3-48.1)	0.09
2	43.5 (32.0-55.0)
3	22.9 (13.2-32.5)
4 and more	27.7 (15.6-39.8)
Isolated liver metastasis
No	35.7 (28.8-42.6)	0.22
Yes	45.3 (37.6-53.0)	0.22
History of metastasectomy
No	32.0 (25.0-38.9)	0.02^a	Ref
Yes	50.4 (39.1-61.7)	0.02^a	0.92 (0.59-1.43)	0.72
Tumor location
Right side colon cancer	31.9 (17.1-46.6)	0.29
Left side colon cancer	45.2 (30.6-59.8)
Rectum cancer	38.3 (28.7-47.9)
KRAS
Wild	30.3 (22.2-38.4)	0.05
Mutant	47.1 (35.6-58.6)
Unknown	48.3 (33.8-62.8)
NRAS
Wild	32.4 (25.4-39.3)	0.004^a	Ref
Mutant	59.9 (-)		0.50 (0.22-1.10)	0.09
Unknown	56.6 (44.3-68.8)		0.54 (0.29-1.02)	0.06
BRAF
Wild	38.7 (30.4-46.9)	0.06
Mutant	19.6 (5.2-33.9)
Unknown	43.0 (25.8-60.2)
MSI status
Microsatellite stable	39.8 (31.5-48.0)	0.79
MSI-high	45.6 (0.0-91.9)
Unknown	35.7 (24.8-46.6)
Best treatment response
CR	- (-)	< 0.001^a	Ref
PR	45.3 (35.5-55.1)		5.19 (1.60-16.80)	0.006^a
SD	36.7 (24.7-48.7)		6.29 (1.92-20.59)	0.002^a
PD	20.9 (17.7-24.2)		15.73 (4.71-20.59)	< 0.001^a
GPS
0	43.5 (34.2-52.8)	0.006^a	Ref
1	28.7 (21.2-36.2)		1.37 (0.94-1.99)	0.10
2	59.9 (9.9-109.9)		0.69 (0.37-1.27)	0.24
NLR
< 2.76	45.3 (35.0-55.6)	0.005^a	Ref
≥ 2.76	29.4 (24.8-33.9)	0.005^a	1.46 (1.03-2.08)	0.03^a
TMI
< 1.39	45.6 (32.4-58.8)	0.02^a	Ref
≥ 1.39	29.5 (24.3-34.5)	0.02^a	1.43 (0.99-2.06)	0.049^a

^aP < 0.05.

OS: Overall survival; HR: Hazard ratio; CI: Confidence interval; ECOG-PS: Eastern Cooperative Oncology Group Performance Status; BMI: Body mass index; CT: Chemotherapy; MSI: Microsatellite instability; CR: Complete response; PR: Partial remission; SD: Stable disease; PD: Progressive disease; GPS: Glasgow prognostic score; NLR: Neutrophil-to-lymphocyte ratio; TMI: Tumor marker index.

Citation: Ilhan Y, Balcik OY, Guzel HG, Onder AH, Demir B, Baser MN, Karadag I, Ozbay MF, Genc TB, Uzuntas S, Poyrazoglu O, Beypinar I, Ergun Y, Ozturk B. Novel tumor marker index combining carcinoembryonic antigen and carbohydrate antigen 19-9: New prognostic factor for metastatic colorectal cancer. World J Gastrointest Oncol 2025; 17(5): 104341
URL: https://www.wjgnet.com/1948-5204/full/v17/i5/104341.htm
DOI: https://dx.doi.org/10.4251/wjgo.v17.i5.104341