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Establishing next-generation reference intervals for pro-gastrin-releasing peptide using a dynamic modeling approach
Dong Zhu1, Haibin Zhao2, Weicheng Zhang3
1Department of Laboratory Medicine, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, No. 168 Litang Road, Changping District, Beijing, 102218, China. zhudongcherish@163.com.
Journal of Translational Medicine
|September 2, 2025
Summary
Next-generation reference intervals (RIs) for serum pro-gastrin-releasing peptide (ProGRP) improve accuracy in adults. These new RIs better reflect age-related changes than traditional partitioned intervals.
Area of Science:
- Clinical Chemistry
- Biomarker Research
- Geriatric Medicine
Background:
- Serum pro-gastrin-releasing peptide (ProGRP) levels change with age.
- Traditional reference intervals (RIs) do not capture these age-related physiological shifts.
- Novel RIs are needed for accurate ProGRP interpretation in aging populations.
Purpose of the Study:
- To investigate age- and sex-specific ProGRP dynamics in North China adults.
- To develop and validate next-generation RIs for ProGRP.
- To compare the accuracy of next-generation RIs with conventional partitioned RIs.
Main Methods:
- Analyzed ProGRP levels in 4136 individuals aged 20-80 years.
- Used statistical tests to assess age and sex effects on ProGRP.
- Developed next-generation RIs using generalized additive models and visualized age-related dynamics.
- Evaluated RI clinical applicability by comparing upper reference limit flagging rates.
Main Results:
- ProGRP levels showed minimal sex influence but significant age-related increases after age 40.
- Next-generation RIs demonstrated improved accuracy and stability compared to partitioned RIs.
- Flagging rates with next-generation RIs were closer to the theoretical 2.5% across age groups.
Conclusions:
- Next-generation RIs enhance the accuracy of ProGRP laboratory result interpretation.
- These advanced RIs better account for age-related physiological changes.
- Wider clinical adoption of next-generation RIs is expected with improved laboratory informatics.

