Zhang Miao-Miao, Zhu Dong, Zhao Hai-Bin, Zhao Xiu-Ying
Department of Laboratory Medicine, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing 102218, China.
World J Gastroenterol. 2025 Aug 21;31(31):108977. doi: 10.3748/wjg.v31.i31.108977.
Pepsinogen (PG) and the PG I/II ratio (PGR) are critical indicators for diagnosing infection and chronic atrophic gastritis, and assessing gastric cancer risk. Existing reference intervals (RIs) often overlook age, sex, and demographic variations. Partitioned RIs, while considering these factors, fail to capture the gradual age-related physiological changes. Next-generation RIs offer a solution to this limitation.
To investigate age- and sex-specific dynamics of PG and establish next-generation RIs for adults and the elderly in northern China.
After screening, 708 healthy individuals were included in this observational study. Serum PG was measured using chemiluminescence immunoassay. Age- and sex-related effects on PG were analyzed with a two-way analysis of variance. RI partitioning was determined by the standard deviation ratio (SDR). Traditional RIs were established using a non-parametric approach. Generalized Additive Models for Location, Scale, and Shape (GAMLSS) modeled age-related trends and continuous reference percentiles for PG I and PG II. Reference limit flagging rates for both RI types were compared.
PG I and PG II levels were influenced by age ( < 0.001) and sex ( < 0.001), while PGR remained stable. Age-specific RIs were required for PG I (SDR = 0.366) and PG II (SDR = 0.424). Partitioned RIs were established for PG I and PG II, with a single RI for PGR. GAMLSS modeling revealed distinct age-dependent trajectories: PG I increased from a median of 39.75 μg/L at age 20 years to 49.75 μg/L at age 60 years, a 25.16% increase, after which it plateaued through age 80 years. In contrast, PG II showed a continuous rise throughout the age range, with the median value increasing from 5.07 μg/L at age 20 years to 8.36 μg/L at age 80 years, corresponding to a 64.89% increase. Continuous reference percentiles intuitively reflected these trends and were detailed in this study. Next-generation RIs demonstrated superior accuracy compared to partitioned RIs when applied to specific age subgroups.
This study elucidates the age- and sex-specific dynamics of PG and, to our knowledge, is the first to establish next-generation RIs for PG, supporting more individualized interpretation in laboratory medicine.
胃蛋白酶原（PG）和PG I/II比值（PGR）是诊断感染和慢性萎缩性胃炎以及评估胃癌风险的关键指标。现有的参考区间（RI）常常忽略年龄、性别和人口统计学差异。分区RI虽然考虑了这些因素，但未能捕捉与年龄相关的渐进性生理变化。新一代RI解决了这一局限性。
研究PG的年龄和性别特异性动态变化，并为中国北方成年人和老年人建立新一代RI。
经过筛选，708名健康个体纳入本观察性研究。采用化学发光免疫分析法检测血清PG。采用双向方差分析分析年龄和性别对PG的影响。RI分区由标准差比（SDR）确定。采用非参数方法建立传统RI。位置、尺度和形状的广义相加模型（GAMLSS）对PG I和PG II的年龄相关趋势和连续参考百分位数进行建模。比较两种RI类型的参考限值标记率。
PG I和PG II水平受年龄（<0.001）和性别（<0.001）影响，而PGR保持稳定。PG I（SDR = 0.366）和PG II（SDR = 0.424）需要年龄特异性RI。为PG I和PG II建立了分区RI，PGR采用单一RI。GAMLSS建模揭示了不同的年龄依赖性轨迹：PG I从20岁时的中位数39.75μg/L增加到60岁时的49.75μg/L，增加了25.16%，此后在80岁时趋于平稳。相比之下，PG II在整个年龄范围内持续上升，中位数从20岁时的5.07μg/L增加到80岁时的8.36μg/L，增幅为64.89%。连续参考百分位数直观地反映了这些趋势，并在本研究中进行了详细说明。当应用于特定年龄亚组时，新一代RI显示出比分区RI更高的准确性。
本研究阐明了PG的年龄和性别特异性动态变化，据我们所知，这是首次为PG建立新一代RI，支持在检验医学中进行更个体化的解读。
