Validation of serum tumor biomarkers in predicting advanced cystic mucinous neoplasm of the pancreas

Table 1 Baseline characteristics and performance of each serum tumor maker in predicting advanced cystic mucinous neoplasms

	Overall	Benign	Advanced	P value1
Patients characteristics (n = 187)
Male (n, %)	109 (58.3)	63 (54.8)	46 (63.9)	0.007
Age (Median, IQR)	62 (54-68)	61 (51-68)	63.5 (56-70)	0.014
Cyst size (Median, IQR, mm)	28.5 (19-42)	24.5 (15-37)	38.5 (28-59.5)	< 0.0001
Location (H/B/T/D)	111/31/30/15	63/20/20/10	48/11/10/5
CA19-9 (n = 187)
Median, IQR (U/mL)	10.11(4.4-52.9)	7.1(3.4-16.3)	55.5 (9.3-319.3)	< 0.0001
≥ 37/< 37 U/mL	50/137	11/104	39/33	< 0.0001
CEA (n = 187)
Median, IQR (ng/mL)	2.37 (1.54-3.98)	2.23 (1.5-3.3)	3.1 (2.02-5.2)	< 0.0001
≥ 5/< 5 ng/mL	27/160	9/106	18/54	0.001
CA125 (n = 135)
Median, IQR (U/mL)	12.2 (8.2-18.8)	12.1 (7.0-16.8)	12.75 (8.9-23.4)	0.002
≥ 35 /< 35 U/mL	10/125	1/82	9/43	0.002
CA724 (n = 116)
Median, IQR (U/mL)	1.6 (1.025-3.15)	1.44 (1.0-2.66)	2.4 (1.07-6.8)	0.014
≥ 9.8/< 9.8 U /mL	10/106	3/70	7/36	0.05
CA242 (n = 31)
Median, IQR (U/mL)	7.13 (3.6-12.7)	5.35 (2.7-7.9)	11.1 (6.95-31.7)	0.136
≥ 20/< 20 U/mL	6/25	1/15	5/10	0.08

¹P values were based on student’s t test comparing mean values of each serum tumor maker. cMN: Cystic mucinous neoplasm; IQR: Interquartile range; CEA: carcinoembryonic antigen; CA: Carbohydrate antigen.

Table 2 Performance of five serum tumor makers in predicting advanced cystic mucinous neoplasms

	SE (95%CI)	SP (95%CI)	PPV (95%CI)	NPV (95%CI)	AC	AUC	P value
CA19-9 (%)	54.2 (42.1-65.8)	90.4 (83.2-94.5)	78 (63.6.7-88)	75.9 (67.7-82.6)	76.5	0.766
CEA (%)	25 (15.9-45.9)	92.17 (85.26-96.13)	66.67 (46-82.8)	66.3 (58.3-73.4)	66.31	0.651	0.04
CA125 (%)	17.3 (8.7-30.8)	98.8 (92.54-99.9)	90 (54.1-99.5)	65.5 (56.5-73.7)	67.4	0.583	0.004
CA724 (%)	16.3 (7.3-31.3)	95.9 (87.7-98.9)	70 (35.4-91.9)	66 (56.1-74.8)	66.4	0.618	0.03
CA242 (%)	31.25 (12.1-58.5)	93.3 (66-99.7)	83.3 (36.5-99.1)	56 (35.3-75)	61.3	0.758	0.81
CA199 ± any one of other STMs	62.5 (50.3-73.4)	83.5 (75.1-89.5)	70.3 (57.4-80.8)	78 (69.5-84.8)	75.4	0.715	0.32

P value: Comparison results of areas under curves for carbohydrate antigen 19-9 and other serum tumor makers in predicting advanced-cystic mucinous neoplasms. SE: Sensitivity; SP: Specificity; PPV: Positive predictive value; NPV: Negative predictive value. AC: Accuracy; AUC: Area under curve; CA: Carbohydrate antigen; STM: Serum tumor maker.

Table 3 Receiver operating characteristic curve comparison analyses of each serum tumor marker

ROC curve	ΔAUC1	Standard error	Z statistic	P value
CA19-9 vs CEA	0.115	0.038 and 0.042	2.03	0.04
CA19-9 vs CA125	0.183	0.038 and 0.051	2.88	0.004
CA19-9 vs CA724	0.148	0.038 and 0.058	2.14	0.03
CA19-9 vs CA242	0.008	0.038 and 0.090	0.08	0.81
CEA vs CA125	0.068	0.042 and 0.051	1.03	0.30
CEA vs CA724	0.033	0.042 and 0.058	0.46	0.62
CA125 vs CA724	0.035	0.051 and 0.058	0.45	0.63

¹ΔAUC: The gap between the two areas under the curves. CA: Carbohydrate antigen; CEA: Carcinoembryonic antigen; ROC: Receiver operating characteristic; AUC: Area under curve.

Table 4 Performance of each serum tumor maker in predicting advanced intraductal papillary mucinous neoplasms

	Overall	Benign	Advanced	P value1
CA19-9 (n = 151)
Median, IQR (U/mL)	9.7 (3.75-46.3)	6.05 (3.1-15.2)	46.3 (9.0-166.4)	< 0.0001
≥ 37/< 37 U/mL	40/111	9/83	31/8	< 0.0001
CEA (n = 151)
Median, IQR (ng/mL)	2.7 (1.85-4.16)	2.46 (1.67-3.44)	3.1 (2.05-5.3)	0.002
≥ 5/< 5 ng/mL	24/127	9/83	15/44	0.01
CA125 (n = 109)
Median, IQR (U/mL)	11.9 (8.0-17.35)	11.65 (6.8-16.6)	12.1 (8.7-18.8)	0.051
≥ 35 /< 35 U/mL	5/104	1/63	4/41	0.182
CA724 (n = 96)
Median, IQR (U/mL)	1.64 (1.04-3.17)	1.44 (1.02-2.7)	2.5 (1.16-6.8)	0.022
≥ 9.8/< 9.8 U /mL	9/87	2/56	7/31	0.035
CA242 (n = 28)
Median, IQR (U/mL)	7.44 (4.1-12.7)	5.7 (3.6-8.23)	9.8 (6.9-20.7)	0.174
≥ 20/< 20 U/mL	5/23	1/12	4/11	0.416

¹P values were based on student’s t test comparing mean values of each serum tumor maker. CA: Carbohydrate antigen; CEA: Carcinoembryonic antigen; IQR: Interquartile range.

Table 5 Performance of each serum tumor maker in predicting advanced mucinous cystic neoplasms

	Overall	Benign	Advanced	P value1
CA19-9 (n = 31)
Median, IQR (U/mL)	14.7 (7.3-108.1)	7.73 (5.63-24.2)	157 (15.7-1100)	0.001
≥ 37/< 37 U/mL	10/26	2/21	8/5	0.003
CEA (n = 31)
Median, IQR (ng/mL)	1.5 (1.05-2.58)	1.5 (1.0-1.87)	2.56 (1.31-5.57)	0.004
≥ 5/< 5 ng/mL	3/33	0/23	3/10	0.04
CA125 (n = 26)
Median, IQR (U/mL)	14.5 (10.0-25.7)	14.4 (9.2-20.1)	68.6 (11.9-125)	< 0.0001
≥ 35 /< 35 U/mL	5/21	0/19	5/2	< 0.0001
CA724 (n = 20)
Median, IQR (U/mL)	1.5 (0.96-2.7)	1.52 (0.99-2.24)	1.53 (0.8-6.8)	0.538
≥ 9.8/< 9.8 U /mL	1/19	1/14	0/5	1.00
CA242 (n = 3)
Median, IQR (U/mL)	2.39 (0.1)	1.25 (0.1)	35.35	Not applicable
≥ 20/< 20 U/mL	1/2	0/2	1/0	0.333

¹P values were based on student’s t test comparing mean values of each serum tumor maker. CA: Carbohydrate antigen; CEA: Carcinoembryonic antigen; IQR: Interquartile range.

Table 6 Comparison of serum carbohydrate antigen 125 levels in mucinous cystic neoplasms and intraductal papillary mucinous neoplasms

	Overall	Benign	Advanced
mean ± SD (U/mL) (IPMN)	14.6 ± 12.2	12.7 ± 7.56	17.3 ± 16.4
mean ± SD (U/mL) (MCN)	30.5 ± 40.5	14.3 ± 6.4	74.4 ± 60.3
Comparison P value	0.001	0.69	< 0.0001
≥ 35/< 35 U/mL (IPMN)	5/104	1/63	4/41
≥ 35/< 35 U/mL (MCN)	5/21	0/19	5/2
Comparison P value	0.03	1.00	< 0.0001

MCN: Mucinous cystic neoplasm; SD: Standard deviation; IPMN: Intraductal papillary mucinous neoplasm.