Perioperative serum carcinoembryonic antigen: Powerful marker for prognostic prediction and adjuvant chemotherapy decision-making in patients with stage II and III colorectal cancer

doi:10.3748/wjg.v32.i9.114200

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World Journal of Gastroenterology

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World J Gastroenterol. Mar 7, 2026; 32(9): 114200
Published online Mar 7, 2026. doi: 10.3748/wjg.v32.i9.114200

Table 1 Clinicopathological characteristics of patients, n (%)

Characteristics	Training cohort (n = 2496)	Validation cohort (n = 1293)	P value
Sex			0.518
Male	1513 (60.6)	769 (59.5)
Female	983 (39.4)	524 (40.5)
Age, mean (SD)	65.64 (10.14)	60.73 (10.33)	< 0.001
Height, mean (SD)	166.37 (9.16)	167.52 (28.99)	0.069
Weight, mean (SD)	66.58 (12.43)	66.25 (11.90)	0.432
Smoking			< 0.001
Negative	1370 (54.9)	889 (68.8)
Positive	1126 (45.1)	404 (31.2)
Drinking			0.853
Negative	1963 (78.6)	1021 (79.0)
Positive	533 (21.4)	272 (21.0)
Ileus			< 0.001
Negative	2139 (85.7)	1181 (91.3)
Positive	357 (14.3)	112 (8.7)
Diabetes			< 0.001
Negative	2338 (93.7)	1159 (89.6)
Positive	158 (6.3)	134 (10.4)
Hypertension			< 0.001
Negative	2304 (92.3)	1013 (78.3)
Positive	192 (7.7)	280 (21.7)
Differentiation			< 0.001
Well	7 (0.3)	173 (13.4)
Moderate	2060 (82.5)	1023 (79.1)
Poor	429 (17.2)	97 (7.5)
Signet-ring cell carcinoma			0.022
Negative	2444 (97.9)	1280 (99.0)
Positive	52 (2.1)	13 (1.0)
Mucinous carcinoma			< 0.001
Negative	2060 (82.5)	1132 (87.5)
Positive	436 (17.5)	161 (12.5)
Location			< 0.001
Rectum	1232 (49.4)	797 (61.6)
Left colon	684 (27.4)	267 (20.6)
Right colon	580 (23.2)	229 (17.7)
Vascular cancer embolus			0.051
Negative	2260 (90.5)	1196 (92.5)
Positive	236 (9.5)	97 (7.5)
Perineural invasion			0.397
Negative	2056 (82.4)	1080 (83.5)
Positive	440 (17.6)	213 (16.5)
Stage			< 0.001
II	1285 (51.5)	780 (60.3)
III	1211 (48.5)	513 (39.7)
Microsatellite stability			< 0.001
MSI-H	178 (7.1)	30 (2.3)
MSS	804 (32.2)	504 (39.0)
No detection	1514 (60.7)	759 (58.7)
Recurrence or metastasis site			0.002
No recurrence or metastasis	2158 (86.5)	1171 (90.6)
Liver	121 (4.8)	52 (4.0)
Lung	101 (4.0)	32 (2.5)
Recurrence	25 (1.0)	14 (1.1)
Abdominal pelvic and viscera in abdominal pelvic	46 (1.8)	16 (1.2)
Others (brain, bone, superficial lymph nodes, etc.)	45 (1.8)	8 (0.6)
Adjuvant chemotherapy type			< 0.001
Folfox	134 (5.4)	254 (19.6)
Xelox	981 (39.3)	391 (30.2)
Monotherapy	105 (4.2)	191 (14.8)
No adjuvant chemotherapy	1276 (51.1)	457 (35.3)

MSI-H: Microsatellite instability-high; MSS: Microsatellite stable.

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Table 2 Univariate and multivariate stepwise Cox regression analysis (stepped by Akaike information criterion) of overall survival in training cohort

Variables	Level	Univariate analysis			Multivariate analysis
	Level	HR	95%CI	P value	HR	95%CI	P value
Sex	Female (reference = male)	0.9630	0.8180-1.1300	0.6550
Age	Age (continuous)	1.0300	1.0200-1.0400	< 0.001	1.0330	1.0234-1.0417	< 0.001
Weight	Weight (continuous)	0.9980	0.9920-1.0000	0.5340
Height	Height (continuous)	1.0000	0.9950-1.0100	0.4010	1.0072	0.9987-1.0158	0.0950
Smoking	Positive (reference = negative)	1.0100	0.8620-1.1900	0.8890
Drinking	Positive (reference = negative)	1.1400	0.9460-1.3700	0.1690
Ileus	Positive (reference = negative)	1.3600	1.1100-1.6700	0.0032	1.3589	1.1019-1.6758	0.0041
Diabetes	Positive (reference = negative)	1.6000	1.2200-2.0900	0.0006
Hypertension	Positive (reference = negative)	1.2100	0.9210-1.5800	0.1730
Differentiation	Moderate (reference = well)	0.6260	0.2010-1.9500	0.4190	0.6163	0.1971-1.9266	0.4052
Differentiation	Poor (reference = well)	0.9190	0.2920-2.8900	0.8850	0.8002	0.2535-2.5260	0.7039
Signet-ring cell carcinoma	Positive (reference = negative)	1.8500	1.1700-2.9100	0.0086
Mucinous carcinoma	Positive (reference = negative)	1.2300	1.0100-1.5000	0.0417	1.2369	1.0115-1.5125	0.0383
Location	Left colon (reference = rectum)	0.7820	0.6470-0.9450	0.0110	0.7762	0.6404-0.9407	0.0098
Location	Right colon (reference = rectum)	0.7540	0.6120-0.9290	0.0081	0.7744	0.6256-0.9586	0.0189
Perineural invasion	Positive (reference = negative)	1.8700	1.560-2.2400	< 0.001	1.6107	1.3309-1.9492	< 0.001
Vascular cancer embolus	Positive (reference = negative)	1.8700	1.4900-2.3400	< 0.001	1.3868	1.0981-1.7514	0.0060
Microsatellite stability	MSS (reference = MSI-H)	1.1100	0.7610-1.6100	0.5940
Microsatellite stability	No detection (reference = MSI-H)	1.6500	1.1600-2.3600	0.0056
AJCC stage	Stage III (reference = stage II)	1.9300	1.6400-2.2700	< 0.001	1.6919	1.4248-2.0090	< 0.001
Pre-CEA	Pre-CEA (continuous)	1.0030	1.0020-1.0040	< 0.001
Post-CEA	Post-CEA (continuous)	1.0010	1.0010-1.0010	< 0.001	1.0008	1.0004-1.0012	< 0.001
Pre-CA 19-9	Pre-CA 19-9 (continuous)	1.0000	1.000-1.000	0.0001
Post-CA19-9	Post-CA 19-9 (continuous)	1.0000	1.000-1.000	< 0.001

pre-CEA: Preoperative carcinoembryonic antigen; post-CEA: Postoperative carcinoembryonic antigen; AJCC: American Joint Committee on Cancer; CI: Confidence interval; HR: Hazard ratio; MSI-H: Microsatellite instability-high; MSS: Microsatellite stable.

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Table 3 Univariate and multivariate stepwise Cox regression analysis (stepped by Akaike information criterion) of disease-free survival in training cohort

Variables	Level	Univariate analysis			Multivariate analysis
	Level	HR	95%CI	P value	HR	95%CI	P value
Sex	Female (reference = male)	0.9560	0.8220-1.1100	0.5560
Age	Age (continuous)	1.0200	1.0100-1.0300	< 0.001	1.0219	1.0141-1.0298	< 0.001
Weight	Weight (continuous)	1.0000	0.9950-1.0100	0.9010
Height	Height (continuous)	1.0100	0.9970-1.0100	0.1810	1.0087	1.0004-1.0171	0.0411
Smoking	Positive (reference = negative)	0.9490	0.8190-1.1000	0.4880
Drinking	Positive (reference = negative)	1.1800	0.9950-1.4000	0.0564
Ileus	Positive (reference = negative)	1.4800	1.2300-1.7900	< 0.001	1.4622	1.2071-1.7712	0.0001
Diabetes	Positive (reference = negative)	1.9400	1.5300-2.4600	< 0.001	1.5164	1.1925-1.9285	0.0007
Hypertension	Positive (reference = negative)	1.4300	1.1300-1.8200	0.0034
Differentiation	Moderate (reference = well)	0.7580	0.2430-2.3600	0.6320	0.7395	0.2368-2.3092	0.6035
Differentiation	Poor (reference = well)	1.1000	0.3500-3.4400	0.8740	0.9363	0.2974-2.9481	0.9105
Signet-ring cell carcinoma	Positive (reference = negative)	1.8000	1.1700-2.7800	0.0078
Mucinous carcinoma	Positive (reference = negative)	1.2400	1.0300-1.4900	0.0206	1.2125	1.0070-1.4599	0.0420
Location	Left colon (reference = rectum)	0.8000	0.6720-0.9520	0.0122	0.7983	0.6689-0.9528	0.0126
Location	Right colon (reference = rectum)	0.7800	0.6440-0.9440	0.0107	0.7979	0.6553-0.9715	0.0246
Perineural invasion	Positive (reference = negative)	1.7900	1.5100-2.1300	< 0.001	1.5455	1.2952-1.8441	< 0.001
Vascular cancer embolus	Positive (reference = negative)	1.6700	1.3500-2.0700	< 0.001	1.2415	0.9940-1.5506	0.0565
Microsatellite stability	MSS (reference = MSI-H)	1.1000	0.7800-1.5600	0.5810
Microsatellite stability	No detection (reference = MSI-H)	1.6700	1.2100-2.3200	0.0020
AJCC stage	Stage III (reference = stage II)	1.9800	1.7000-2.3000	< 0.001	1.7244	1.4716-2.0205	< 0.001
Pre-CEA	Pre-CEA (continuous)	1.0030	1.0020-1.0040	< 0.001
Post-CEA	Post-CEA (continuous)	1.0010	1.0010-1.0020	< 0.001	1.0007	1.0002-1.0011	0.0022
Pre-CA 19-9	Pre-CA 19-9 (continuous)	1.0000	1.0000-1.0000	< 0.001	1.0006	1.0000-1.0013	0.0578
Post-CA 19-9	Post-CA 19-9 (continuous)	1.0000	1.0000-1.0000	< 0.001

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Table 4 Univariate and multivariate stepwise Cox regression analysis (stepped by Akaike information criterion) analyses of overall survival in validation cohort

Variables	Level	Univariate analysis			Multivariate analysis
Variables	Level	HR	95%CI	P value	HR	95%CI	P value
Sex	Female (reference = male)	0.9700	0.7330-1.2900	0.8340
Age	Age (continuous)	1.0400	1.0200-1.0500	< 0.001	1.0339	1.0192-1.0489	< 0.001
Weight	Weight (continuous)	0.9930	0.9800-1.0000	0.2410
Height	Height (continuous)	0.9780	0.9610-0.9960	0.0191	0.9828	0.9649-1.0011	0.0650
Smoking	Positive (reference = negative)	0.9580	0.7070-1.3000	0.7840
Drinking	Positive (reference = negative)	0.7210	0.4920-1.0600	0.0946
Ileus	Positive (reference = negative)	1.2500	0.8420-1.8500	0.2680	1.5257	0.9942-2.3413	0.0532
Diabetes	Positive (reference = negative)	1.5100	1.0200-2.2600	0.0420
Hypertension	Positive (reference = negative)	1.4300	1.0500-1.9700	0.0256
Differentiation	Moderate (reference = well)	0.4860	0.3470-0.6820	< 0.001	0.5418	0.3803-0.7720	0.0007
Differentiation	Poor (reference = well)	0.6200	0.3450-1.1100	0.1100	0.8004	0.4386-1.4608	0.4683
Signet-ring cell carcinoma	Positive (reference = negative)	5.2500	2.4600-11.200	< 0.001
Mucinous carcinoma	Positive (reference = negative)	1.1200	0.7730-1.6100	0.5590	1.0618	0.7103-1.5873	0.7699
Location	Left colon (reference = rectum)	0.8850	0.6230-1.2600	0.4950	0.8688	0.5923-1.2744	0.4718
Location	Right colon (reference = rectum)	1.0900	0.7730-1.5500	0.6130	0.9103	0.6058-1.3680	0.6512
Perineural invasion	Positive (reference = negative)	1.4300	1.0200-2.0200	0.0403	1.1350	0.7867-1.6376	0.4982
Vascular cancer embolus	Positive (reference = negative)	2.5600	1.7400-3.7500	< 0.001	1.9304	1.2780-2.9159	0.0018
Microsatellite stability	MSS (reference = MSI-H)	0.5320	0.2400-1.1800	0.1200
Microsatellite stability	No detection (reference = MSI-H)	0.7360	0.3440-1.5700	0.4270
AJCC stage	Stage III (reference = stage II)	2.0500	1.5500-2.7100	< 0.001	1.7645	1.3127-2.3717	0.0002
Pre-CEA	Pre-CEA (continuous)	1.0030	1.0020-1.0040	< 0.001
Post-CEA	Post-CEA (continuous)	1.0020	1.001-1.0030	0.0005	1.0015	1.0004-1.0025	0.0058
Pre-CA 19-9	Pre-CA 19-9 (continuous)	1.0000	1.0000-1.0000	< 0.001
Post-CA 19-9	Post-CA 19-9 (continuous)	1.0000	1.0000-1.0000	< 0.001

Full Size Table

Table 5 Univariate and multivariate stepwise Cox regression analysis (stepped by Akaike information criterion) of disease-free survival in validation cohort

Variables	Level	Univariate analysis			Multivariate analysis
Variables	Level	HR	95%CI	P value	HR	95%CI	P value
Sex	Female (reference = male)	1.1300	0.8830-1.4500	0.3300
Age	Age (continuous)	1.0300	1.0200-1.0400	< 0.001	1.0268	1.0140-1.0398	< 0.001
Weight	Weight (continuous)	0.9910	0.9800-1.0000	0.0908
Height	Height (continuous)	0.9770	0.9610-0.9920	0.0034	0.9783	0.9624-0.9944	0.0084
Smoking	Positive (reference = negative)	0.9360	0.7140-1.2300	0.6330
Drinking	Positive (reference = negative)	0.7840	0.5630-1.0900	0.1500
Ileus	Positive (reference = negative)	1.3000	0.9090-1.8600	0.1500	1.5541	1.0495-2.3014	0.0277
Diabetes	Positive (reference = negative)	1.5400	1.0800-2.2000	0.0163	1.3728	0.9581-1.9672	0.0842
Hypertension	Positive (reference = negative)	1.4600	1.1100-1.9400	0.0076
Differentiation	Moderate (reference = well)	0.5430	0.3990-0.7390	0.0001	0.6312	0.4566-0.8726	0.0054
Differentiation	Poor (reference = well)	0.7020	0.4190-1.1800	0.1790	0.9253	0.5435-1.5752	0.7748
Signet-ring cell carcinoma	Positive (reference = negative)	3.3600	1.5800-7.1200	0.0016
Mucinous carcinoma	Positive (reference = negative)	0.9560	0.6750-1.3500	0.8010
Location	Left colon (reference = rectum)	0.9310	0.6820-1.2700	0.6550	0.9343	0.6638-1.3148	0.6965
Location	Right colon (reference = rectum)	1.0100	0.7370-1.3900	0.9350	0.9149	0.6299-1.3287	0.6403
Perineural invasion	Positive (reference = negative)	1.3500	0.9910-1.8400	0.0573	1.1080	0.7997-1.5350	0.5377
Vascular cancer embolus	Positive (reference = negative)	2.2500	1.5700-3.2300	< 0.001	1.8155	1.2354-2.6679	0.0024
Microsatellite stability	MSS (reference = MSI-H)	0.6150	0.2960-1.2800	0.1930
Microsatellite stability	No detection (reference = MSI-H)	0.7550	0.3710-1.5300	0.4370
AJCC stage	Stage III (reference = stage II)	1.8800	1.4600-2.4100	< 0.001	1.6515	1.2721-2.1439	0.0002
Pre-CEA	Pre-CEA (continuous)	1.0030	1.0010-1.0040	< 0.001
Post-CEA	Post-CEA (continuous)	1.0010	1.0010-1.0020	0.0007	1.0012	1.0003-1.0022	0.0100
Pre-CA 19-9	Pre-CA 19-9 (continuous)	1.0000	1.0000-1.0000	< 0.001	1.0014	1.0005-1.0024	0.0041
Post-CA 19-9	Post-CA 19-9 (continuous)	1.0000	1.0000-1.0000	< 0.001

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Table 6 Recurrence or metastasis rates in different carcinoembryonic antigen level

Level	Recurrence or metastasis rate in training cohort (%)	Recurrence or metastasis rate in validation cohort (%)
Elevated pre-CEA	17.92	10.61
Normal pre-CEA	10.69	8.74
Elevated post-CEA	27.58	19.13
Normal post-CEA	11.04	7.75
Total	13.42	9.36

pre-CEA: Preoperative carcinoembryonic antigen; post-CEA: Postoperative carcinoembryonic antigen.

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Citation: Du FQ, Liu JL, Mai LD, Han XH, Song WJ, Yang D, Zhang QJ, Zhang R, Liu YL, Tong JX. Perioperative serum carcinoembryonic antigen: Powerful marker for prognostic prediction and adjuvant chemotherapy decision-making in patients with stage II and III colorectal cancer. World J Gastroenterol 2026; 32(9): 114200
URL: https://www.wjgnet.com/1007-9327/full/v32/i9/114200.htm
DOI: https://dx.doi.org/10.3748/wjg.v32.i9.114200