Age- and gender-specific dynamics and next-generation reference intervals for pepsinogen in northern China

Table 1 Baseline characteristics of enrolled subjects, mean ± SD/median (interquartile range) or n (%)

Variable	Value
Age, years	45 (35-54)
Age group, years
20-29	73 (10.3)
30-39	173 (24.4)
40-49	207 (29.2)
50-59	142 (20.1)
≥ 60	113 (16.0)
Sex (male/female)	417 (58.9)/291 (41.1)
PG I (μg/L)	44.0 (36.7-54.0)
PG II (μg/L)	5.9 (4.8-7.3)
CEA (ng/mL)	2.41 (2.05-2.98)
CA724 (KU/L)	1.87 (1.22-3.21)
ALT (U/L)	18.5 (13.3-27.9)
AST (U/L)	19.2 (16.4-23.2)
GGT (U/L)	21.0 (14.0-34.0)
CREA (µmol/L)	76.0 (67.0-88.0)
WBC (× 109/L)	5.5 (4.7-6.5)
Hb (g/L)	147.0 (134.0-157.0)

Continuous variables are presented as mean ± SD or median (IQR), depending on the data distribution. Categorical variables are reported as number (percentage). CEA: Carcinoembryonic antigen; CA724: Carbohydrate antigen 724; PG: Pepsinogen; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GGT: Gamma-glutamyl transferase; CREA: Creatinine; WBC: White blood cell; Hb: Hemoglobin; IQR: Interquartile range.

Table 2 Pairwise comparison of pepsinogen I and pepsinogen II levels among different age groups

Comparison groups (age, years)	P value
	PG I	PG II
20-29 vs 30-39	1	1
20-29 vs 40-49	0.82	0.266
20-29 vs 50-59	0.001	< 0.001
20-29 vs 60+	< 0.001	< 0.001
30-39 vs 40-49	0.296	0.144
30-39 vs 50-59	< 0.001	< 0.001
30-39 vs 60+	< 0.001	< 0.001
40-49 vs 50-59	0.001	< 0.001
40-49 vs 60+	< 0.001	< 0.001
50-59 vs 60+	0.325	0.057

PG: Pepsinogen.

Table 3 Next-generation reference intervals for pepsinogen I and pepsinogen II

Age (years)	PG I (μg/L)			PG II (μg/L)
	2.5th percentile	Median	97.5th percentile	2.5th percentile	Median	97.5th percentile
20	23.08	39.75	60.3	3.09	5.07	7.92
21	23.7	39.87	60.73	3.11	5.08	8.02
22	23.71	39.98	61.17	3.13	5.1	8.13
23	23.71	40.1	61.62	3.14	5.12	8.23
24	23.72	40.21	62.06	3.16	5.13	8.32
25	23.74	40.32	62.49	3.17	5.15	8.43
26	23.75	40.41	62.92	3.19	5.16	8.53
27	23.77	40.5	63.34	3.2	5.18	8.65
28	23.79	40.58	63.76	3.21	5.19	8.8
29	23.66	40.65	64.15	3.23	5.21	8.94
30	23.63	40.72	64.55	3.25	5.23	9.09
31	23.59	40.79	64.95	3.26	5.25	9.23
32	23.56	40.86	65.33	3.28	5.27	9.42
33	23.53	40.95	65.73	3.3	5.29	9.58
34	23.52	41.04	66.11	3.32	5.31	9.74
35	23.52	41.16	66.48	3.33	5.33	9.89
36	23.53	41.29	66.85	3.35	5.37	10.03
37	23.56	41.43	67.21	3.37	5.4	10.15
38	23.61	41.6	67.58	3.39	5.43	10.27
39	23.68	41.8	67.95	3.41	5.47	10.37
40	23.79	42.02	68.39	3.43	5.51	10.47
41	23.93	42.27	68.86	3.44	5.56	10.57
42	24.11	42.56	69.37	3.46	5.6	10.68
43	24.33	42.87	69.89	3.48	5.66	10.79
44	24.59	43.22	70.42	3.49	5.71	10.89
45	24.89	43.59	71.18	3.51	5.77	10.99
46	25.22	43.96	71.85	3.52	5.84	11.1
47	25.59	44.4	72.54	3.53	5.9	11.21
48	25.97	44.83	73.29	3.54	5.97	11.31
49	26.37	45.26	73.98	3.55	6.05	11.42
50	26.77	45.7	74.71	3.56	6.12	11.53
51	27.18	46.15	75.43	3.57	6.19	11.64
52	27.59	46.62	76.17	3.58	6.27	11.76
53	27.98	47.08	76.78	3.6	6.36	11.87
54	28.35	47.46	77.38	3.62	6.43	11.98
55	28.71	47.85	77.92	3.64	6.52	12.09
56	29.07	48.26	78.48	3.66	6.59	12.21
57	29.36	48.67	78.82	3.68	6.67	12.32
58	29.65	49.05	79.19	3.71	6.74	12.44
59	29.89	49.41	79.52	3.73	6.82	12.55
60	30.1	49.75	79.89	3.76	6.9	12.67
61	30.28	50.07	80	3.79	6.97	12.78
62	30.42	50.38	80.17	3.81	7.04	12.89
63	30.53	50.67	80.29	3.84	7.11	13
64	30.61	50.95	80.38	3.87	7.18	13.1
65	30.67	51.22	80.44	3.9	7.26	13.2
66	30.73	51.48	80.44	3.93	7.33	13.3
67	30.77	51.73	80.41	3.96	7.4	13.39
68	30.81	51.97	80.34	4	7.47	13.49
69	30.85	52.2	80.21	4.03	7.55	13.59
70	30.9	52.44	80.01	4.08	7.62	13.69
71	30.95	52.67	79.98	4.13	7.69	13.79
72	31.01	52.9	79.84	4.18	7.77	13.88
73	31.07	53.18	79.7	4.23	7.84	13.98
74	31.14	53.35	79.56	4.28	7.91	14.08
75	31.21	53.58	79.42	4.34	7.98	14.17
76	31.28	53.8	79.28	4.39	8.06	14.26
77	31.36	54.02	79.14	4.45	8.13	14.34
78	31.43	54.25	79.02	4.5	8.2	14.43
79	31.51	54.47	78.91	4.56	8.27	14.51
80	31.58	54.7	78.81	4.61	8.36	14.6

PG: Pepsinogen.

Table 4 Comparison of flagging rates between partitioned and next-generation reference intervals across age groups

Age group, years	PG I				PG II
	URL flagging rate (%)		LRL flagging rate (%)		URL flagging rate (%)		LRL flagging rate (%)
	Partitioned	Continuous	Partitioned	Continuous	Partitioned	Continuous	Partitioned	Continuous
20-29	1.37	2.74	2.74	2.74	0	2.78	2.78	2.78
30-39	1.75	2.34	4.09	3.51	2.96	2.96	2.37	2.96
40-49	3.94	1.97	1.48	2.96	3.4	1.94	1.46	1.94
50-59	3.01	3.76	2.26	1.5	1.43	2.14	3.57	3.57
≥ 60	2.04	2.04	3.06	3.06	4.55	2.73	0.91	1.82
Total	2.65	2.51	2.65	2.95	2.73	2.44	2.15	2.58

The upper reference limit/Lower reference limit flagging rate refers to the percentage of test results fall outside the reference limits. PG: Pepsinogen; LRL: Lower reference limit; URL: Upper reference limit.