# Comprehensive biomarker profiling reveals distinct molecular signatures across stone types: a large-scale cross-sectional study in Southern China

**Authors:** Qingjiang Chen, Linliang Huang, Suilin Wang, Daqiang Wei, Jiancai Lu, Xiujing Han, Zhenglin Chang

PMC · DOI: 10.3389/fphys.2025.1612585 · 2025-06-09

## TL;DR

A large study in Southern China found unique blood markers for different types of stones, which could help diagnose them earlier and understand their causes.

## Contribution

The study is the first to identify distinct clinical biomarker patterns specific to different stone types using routine lab parameters.

## Key findings

- Elevated serum creatinine and cystatin C are linked to uric acid stones.
- PSA and monocyte counts are increased in prostatic calculi.
- Gallstones are associated with higher basophils, ceruloplasmin, and immunoglobulin-A levels.

## Abstract

Stone diseases represent a significant global health burden affecting 10%–15% of the population worldwide. Despite advances in diagnostic imaging, current approaches often lack the ability to predict stone formation or differentiate between stone types at early stages.

This retrospective study analyzed data from 61,310 stone patients and 55,010 matched controls using 1:1 propensity score matching. Stone cases were categorized into five major groups and further subdivided by organ system. Comprehensive serum biomarker profiling was conducted using automated biochemistry analyzers.

Urinary system stones constituted the largest proportion (80.97%), followed by biliary system stones (21.12%). The study revealed distinct biomarker signatures: elevated serum creatinine and cystatin C in uric acid stones; increased PSA and monocyte counts in prostatic calculi; elevated β2-microglobulin and total bilirubin in common bile duct stones; and increased basophils, ceruloplasmin, ferritin, immunoglobulin-A, and rheumatoid factor in gallstones.

This study represents the first comprehensive evaluation of stone-specific clinical biomarker patterns derived from routine laboratory parameters, providing potential diagnostic markers for different stone types and suggesting stone-specific pathophysiological mechanisms.

## Linked entities

- **Proteins:** KLK3 (kallikrein related peptidase 3), ferritin (soma ferritin-like)
- **Diseases:** gallstones (MONDO:0005346)

## Full-text entities

- **Genes:** CST3 (cystatin C) [NCBI Gene 1471] {aka ADLDWA, ARMD11, HEL-S-2}, HLA-G (major histocompatibility complex, class I, G) [NCBI Gene 3135] {aka MHC-G}, NPEPPS (aminopeptidase puromycin sensitive) [NCBI Gene 9520] {aka AAP-S, MP100, PSA}, CP (ceruloplasmin) [NCBI Gene 1356] {aka AB073614, CP-2}
- **Diseases:** biliary system stones (MESH:D002137), Urinary system stones (MESH:D014545), common bile duct stones (MESH:D042882), Stone (MESH:D007669), stone formation (MESH:D058426), prostatic calculi (MESH:D011472)
- **Chemicals:** creatinine (MESH:D003404), bilirubin (MESH:D001663)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12183068/full.md

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Source: https://tomesphere.com/paper/PMC12183068