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

Figure 1 Screening procedures and research flow of this study. CEA: Carcinoembryonic antigen; CA724: Carbohydrate antigen 724; PG: Pepsinogen; PGR: Pepsinogen I/II ratio; GAMLSS: Generalized Additive Models for Location, Scale, and Shape; RIs: Reference intervals.

Figure 2 Effects of age and sex on pepsinogen I, pepsinogen II, and pepsinogen I/II ratio levels. A: Pepsinogen (PG) I levels increase significantly with age, with males exhibiting higher levels than females; B: Similarly, PG II levels show an evident increase with age, with males having higher levels; C: PG I/II ratio remains relatively stable across different demographic groups. Although a slight downward trend with age was observed, no statistically significant differences were found. PG: Pepsinogen; PGR: Pepsinogen I/II ratio.

Figure 3 Next-generation reference intervals for pepsinogen I and pepsinogen II. A and B: The figure illustrates age-related trends and next-generation reference intervals (RIs) for (A) pepsinogen (PG) I and (B) PG II, derived using generalized additive models for location, scale, and shape. A: For PG I, the solid line denotes the age-dependent medians (50^th percentiles), showing the central tendency across age. Dashed lines depict the continuous 2.5^th and 97.5^th percentiles, corresponding to the lower and upper reference limits of the next-generation RIs, respectively; B: For PG II, the solid blue lines of the 50^th percentiles show the age-dependent central trend. Dashed lines correspond to the continuous 2.5^th and 97.5^th percentiles, defining the lower and upper reference limits, respectively. These continuous reference percentiles provide a refined framework for interpreting biomarker values. PG: Pepsinogen; RIs: Reference intervals.