Assessment of tumor markers CA 19-9, CEA, CA 125, and CA 242 for the early diagnosis and prognosis prediction of gallbladder cancer

doi:10.4240/wjgs.v14.i11.1272

Advanced Search

BPG is committed to discovery and dissemination of knowledge

Home / Archive / Volume 14, Issue 11

This Article

Academic Content and Language Evaluation of This Article

CrossCheck and Google Search of This Article

Academic Rules and Norms of This Article

Citation of this article

Corresponding Author of This Article

Research Domain of This Article

Article-Type of This Article

Open-Access Policy of This Article

Times Cited Counts in Google of This Article

Number of Hits and Downloads for This Article

Total Article Views (4611)

All Articles published online

The chart showing PDF series, WORD series, HTML series, Figures (1-4) series, Tables (1-9) series.

Item

Count

PDF

190

WORD

HTML

2975

Figures (1-4)

231

Tables (1-9)

191

Sum=3622

Publishing Process of This Article

The chart showing Browse series, Download series.

Item

Count

Browse

286

Download

703

Sum=989

Nov 27, 2022 (publication date) through Nov 12, 2024

Times Cited of This Article

Times Cited (11)

Journal Information of This Article

Publication Name

World Journal of Gastrointestinal Surgery

ISSN

1948-9366

Publisher of This Article

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

Observational Study

World J Gastrointest Surg. Nov 27, 2022; 14(11): 1272-1284
Published online Nov 27, 2022. doi: 10.4240/wjgs.v14.i11.1272

Table 1 Demographic characteristics

Parameters	GBC, n = 80	Benign GB disease, n = 120	Total, n = 200	P value
Age, yr (n = 200)	57.0 (50.2-66.5)	47.0 (34.0-56.0)	52.0 (41.0-60.0)	< 0.001
Sex (n = 200), n (%)				0.951
Men	27 (33.8)	41 (34.2)	68 (34.0)
Women	53 (66.3)	79 (65.8)	132 (66.0)
BMI in kg/m², (mean)	27.06 ± 4.46	26.50 ± 5.6	26.8 ± 4.98	0.229
Hemoglobin in g/dL	11.8 (10.8-12.6)	11.6 (10.2-12.8)	11.75 (10.6-12.70)	0.523
TLC in cells/μL	8075.0 (6759.0-9801.0)	7830.0 (6705.0-8800.0)	7846.0 (6745.0-9440.0)	0.094
Lymphocytes in cells/μL	27.4 (21.2-31.0)	26.9 (22.0-31.0)	27.0 (22.0-31.0)	0.421
Monocytes in cells/mm³	5.7 (3.4-7.9)	6.0 (4.0-7.0)	6.0 (4.0-7.30)	0.604
Neutrophils in cells/mm³	63.1 (58.2-69.6)	63.0 (59.0-67.0)	63.0 (58.92-67.77)	0.816
Eosinophils, %	3.0 (1.2-4.0)	3.5 (2.0-4.4)	3.0 (2.0-4.10)	0.023
Basophils in cells/μL	0.5 (0.3-1.0)	0.4 (0.1-1.0)	0.50 (0.20-1.0)	0.351
Bilirubin in mg/dL
Total	0.9 (0.6-1.2)	0.8 (0.6-1.1)	0.87 (0.64-1.12)	0.251
Direct	0.3 (0.2-0.5)	0.3 (0.2-0.5)	0.30 (0.20-0.52)	0.621
Indirect	0.6 (0.4-0.7)	0.4 (0.3-0.6)	0.50 (0.36-0.65)	0.015
ALP in IU/L	119.5 (80.5-163.2)	109.0 (76.2-136.2)	111.0 (78.0-146.50)	0.019
SGOT in U/L	34.0 (27.2-43.0)	28.0 (24.0-34.0)	31.0 (25.0-36.0)	0.001
SGPT in U/L	27.0 (21.0-36.5)	23.0 (21.0-30.5)	24.0 (21.0-34.0)	0.012
INR	1.1 (1.0-1.1)	1.1 (1.0-1.1)	1.12 (1.10-1.12)	0.158
Serum creatinine in mg/dL	0.8 (0.7-0.9)	0.8 (0.7-0.9)	0.80 (0.68-0.97)	0.459
BUN in mg/dL	12.3 (9.0-14.4)	12.3 (9.9-14.5)	12.30 (5.0-12.0)	0.479
GB wall thickness in mm	12.0 (9.2-15.1)	6.0 (4.0-8.0)	8.0 (5.0-12.0)	< 0.001

Data shown as median (interquartile range), unless otherwise specified. Qualitative data between benign and carcinoma groups were analyzed using Mann-Whitney U-test and quantitative data were compared with the χ² test. ALP: Alkaline phosphate; BUN: Blood urea nitrogen; INR: International normalized ratio; IQR: Interquartile range; SGOT: Serum glutamic oxaloacetic transaminase; SGPT: Serum glutamic pyruvic transaminase; TLC: Total leukocyte count; GB: Gallbladder; GBC: Gallbladder cancer.

Table 2 Association of tumor markers with benign gallbladder disease and gallbladder cancer

All parameters	Benign, n = 120	Carcinoma, n = 80	P value
CA 19-9 in U/mL	3.1 (1.4-19.4)	112.9 (23.3-318.8)	< 0.001
CA 19-9, n (%)
Normal	108 (90.0)	23 (28.7)	< 0.001
Elevated	12 (10.0)	57 (71.3)	< 0.001
CA 125 in U/mL	8.6 (3.1-15.1)	24.5 (12.0-53.3)	< 0.001
CA 125, n (%)
Normal	112 (93.3)	49 (61.3)	< 0.001
Elevated	8 (6.7)	31 (38.8)	< 0.001
CEA in µg/L	2.3 (1.2-3.1)	3.1 (1.8-4.5)	< 0.003
CEA, n (%)
Normal	114 (94)	60 (75)	< 0.003
Elevated	6 (5.9)	20 (25)	< 0.003
CA 242 in U/mL	2.8 (1.5-9.8)	55.5 (32.7-96.5)	< 0.001
CA 242, n (%)
Normal	108 (90.0)	11 (13.7)	< 0.001
Elevated	12 (10.0)	69 (86.3)	< 0.001

Data shown as median (interquartile range). Qualitative data between benign and carcinoma groups were analyzed using Mann-Whitney U-test and quantitative data were compared with the χ² test. CA 19-9: Carbohydrate antigen 19-9; CA 125: Carbohydrate antigen 125; CA 242: Carbohydrate antigen 242; CEA: Carcinoembryonic antigen.

Table 3 Association between tumor markers and clinical characteristics

Characteristics	CA 19-9		P value	CA 125		P value	CEA		P value	CA 242		P value
Characteristics	*Normal, n =* 131**	*Elevated, n =* 69**	P value	*Normal, n =* 161**	*Elevated, n =* 39**	P value	*Normal, n =* 181**	*Elevated, n =* 19**	P value	*Normal, n =* 119**	*Elevated,n =* 81**	P value
Age, yr	49.0 (39.0-59.0)	55.0 (45.0-63.5)	0.009	50.0 (39.0-59.0)	56.0 (50.0-69.0)	0.001	50.0 (40.0-59.5)	56.0 (45.0-65.0)	0.093	48.0 (34.0-56.0)	56.0 (47.5-64.5)	< 0.001
Sex
Male	46 (35.1)	22 (31.9)	0.754	51 (31.7)	17 (43.6)	0.112	62 (34.3)	6 (31.6)	> 0.05	41 (34.5)	27 (33.3)	0.881
Female	85 (64.9)	47 (68.1)	0.754	110 (68.3)	22 (56.4)	0.112	119 (65.7)	13 (68.4)	> 0.05	78 (65.5)	54 (66.7)	0.881
Gallstones
Absent	12 (9.2)	10 (14.5)	0.181	19 (11.8)	3 (7.7)	0.578	21 (11.6)	1 (5.3)	0.701	7 (5.9)	15 (18.5)	0.010
Present	119 (90.8)	59 (85.5)	0.181	142 (88.2)	36 (92.3)	0.578	160 (88.4)	18 (94.7)	0.701	112 (94.1)	66 (81.5)	0.010

Data shown as n (%). Test used: χ² test. CA 19-9: Carbohydrate antigen 19-9; CA 125: Carbohydrate antigen 125; CA 242: Carbohydrate antigen 242; CEA: Carcinoembryonic antigen.

Table 4 Analyses of the sensitivity of tumor markers in different stages of gallbladder cancer

Clinical stages	*Patients, n =* 80**	CA 19-9	CEA	CA 125	CA 242
I	15 (18.6)	10 (66.7)	1 (6.7)	5 (33.3)	13 (86.7)
IIA	13 (16.3)	12 (92.3)	1 (7.7)	5 (38.5)	12 (92.3)
IIB	4 (5.0)	4 (100.0)	0	2 (50.0)	4 (100.0)
IIIA	4 (5.0)	4 (100.0)	0	2 (50.0)	4 (100.0)
IIIB	44 (55.0)	27 (61.3)	8 (18.1)	17 (38.6)	36 (81.8)

Data shown as n (%). CA 19-9: Carbohydrate antigen 19-9; CA 125: Carbohydrate antigen 125; CA 242: Carbohydrate antigen 242; CEA: Carcinoembryonic antigen.

Table 5 Analyses of different combinations of markers in gallbladder cancer diagnosis

Group	n	1 marker	2 markers	3 markers	4 markers
Benign GB disease	120	29 (24.2)	6 (5.0)	1 (0.8)	0
GBC	80	14 (17.5)	27 (33.7)	25 (31.3)	3 (3.8)
Positive likelihood rate		0.5%	4.5%	25%	100%

GB: Gallbladder; GBC: Gallbladder cancer.

Table 6 Performance of markers for predicting gallbladder cancer

Variable	Sensitivity, %	Specificity, %	PPV, %	NPV, %	AUC (95%CI); P value
CA 19-9 (cutoff: 39.21 by ROC)	71.3	90.0	82.6	82.4	0.849 (0.791-0.907); < 0.001
CA 125 (cutoff: 36.00 by ROC)	38.8	93.3	79.5	69.6	0.758 (0.686-0.831); < 0.001
CEA (cutoff: 10.36 by ROC)	12.5	92.5	52.6	61.3	0.623 (0.542-0.703); 0.003
CA 242 (cutoff: 15.10 by ROC)	86.3	90.0	85.2	90.8	0.925 (0.881-0.969); < 0.001

AUC: Area under the curve; CA 19-9: Carbohydrate antigen 19-9; CA 125: Carbohydrate antigen 125; CA 242: Carbohydrate antigen 242; CEA: Carcinoembryonic antigen; NPV: Negative predictive value; PPV: Positive predictive value; ROC: Receiver operating characteristic.

Table 7 Performance of combination of markers for predicting gallbladder cancer

Variable	Sensitivity, %	Specificity, %	PPV, %	NPV, %
Combination of any 2 markers	63.5	95.0	84.6	85.7
Combination of markers CA 19-9 and CA 242, n = 26	83.2	93.3	96.2	83.5
Combination of ≥ 3 markers	35.0	100.0	100.0	69.8

Any two markers: CA 19 -9 and CA 242 (n = 26); CA 19-9 and CEA (n = 3); CA 19-9 and CA 125 (n = 2); CEA and CA 242 (n = 7); CA 125 and CA 242 (n = 1). CA 19-9: Carbohydrate antigen 19-9; CA 125: Carbohydrate antigen 125; CA 242: Carbohydrate antigen 242; CEA: Carcinoembryonic antigen; NPV: Negative predictive value; PPV: Positive predictive value.

Table 8 Correlations between carbohydrate antigen 19-9, carcinoembryonic antigen, carbohydrate antigen 125, and carbohydrate antigen 242 expression and lymph node metastasis

Marker level	*No LNM, n =* 36**	*LNM, n =* 44**	P value
CA 19-9 in U/mL	110.5 (54.2- 176.7)	221.8 (14.9-753.0)	< 0.05
CEA in µg/L	3.2 (1.4-4.0)	3.37 (1.9-6.2)	> 0.05
CA 125 in U/mL	23.0 (21.5-47.3)	33.0 (7.4-64.2)	> 0.05
CA 242 in U/mL	48.5 (36.1-84.7)	92.0 (25.8-112.0)	< 0.05

Data shown as median (interquartile range). Test: Independent sample t-test. CA 19-9: Carbohydrate antigen 19-9; CA 125: Carbohydrate antigen 125; CA 242: Carbohydrate antigen 242; CEA: Carcinoembryonic antigen; LNM: Lymph node metastasis.

Table 9 Cox proportional hazards model for multivariate regression analysis

Prognostic factor	Parameter estimate	Wald χ²	P value	Hazard ratio	95% CI
CA 19-9	0	0.152	0.697	1	0.999-1.001
CEA	-0.137	1.415	0.234	0.872	0.696-1.093
CA 125	0.001	0.211	0.464	1.001	0.995-1.008
CA 242	0.017	10.422	0.001	1.017	1.007-1.027
LNM	-2.06	6.001	0.014	0.127	0.024-0.662
Age	-0.05	2.814	0.093	0.951	0.897-1.009
Sex	-0.264	0.098	0.755	0.768	0.146-4.027
BMI	0.038	0.478	0.489	1.038	0.933-1.155
GB wall thickness	-0.076	2.096	0.148	0.927	0.837-1.027
Stone size	-0.318	2.114	0.146	0.728	0.474-1.117

95%CI: 95% confidence interval; BMI: Body Mass Index; CA 19-9: Carbohydrate antigen 19-9; CA 125: Carbohydrate antigen 125; CA 242: Carbohydrate antigen 242; CEA: Carcinoembryonic antigen; GB: Gallbladder; LNM: Lymph node metastasis.

Citation: Sinha SR, Prakash P, Singh RK, Sinha DK. Assessment of tumor markers CA 19-9, CEA, CA 125, and CA 242 for the early diagnosis and prognosis prediction of gallbladder cancer. World J Gastrointest Surg 2022; 14(11): 1272-1284
URL: https://www.wjgnet.com/1948-9366/full/v14/i11/1272.htm
DOI: https://dx.doi.org/10.4240/wjgs.v14.i11.1272