# Serum-urine metabolic integration via UPLC-QTOF/MS uncovers shared pathway biomarkers for cirrhosis diagnosis

**Authors:** Xiaogang Li, Runxi Wang, Hongbing Zhou, Ruixue Li, Hong Chang, Songli Shi

PMC · DOI: 10.3389/fmed.2025.1646323 · Frontiers in Medicine · 2026-02-09

## TL;DR

This study uses metabolic profiling of serum and urine to identify shared biomarkers and pathways for diagnosing liver cirrhosis.

## Contribution

The study identifies four shared metabolites and three metabolic pathways across serum and urine for noninvasive cirrhosis diagnosis.

## Key findings

- 55 serum and 51 urine metabolites were dysregulated in cirrhosis patients.
- Four shared metabolites were identified in both serum and urine.
- Three co-regulated pathways were linked to cirrhosis progression.

## Abstract

Liver cirrhosis is the terminal stage of chronic liver disease, which is marked by high morbidity and mortality in its advanced phases. Although liver biopsy still serves as the gold - standard diagnostic method, the detection of serum and urine metabolites holds great promise for the identification of cirrhosis.

Untargeted metabolomics analysis was carried out using ultra - performance liquid chromatography coupled with quadrupole time - of - flight mass spectrometry (UPLC - QTOF/MS). We compared the serum and urine metabolic profiles between 30 healthy individuals and 28 liver cirrhosis patients to screen for biomarkers associated with liver cirrhosis.

A total of 55 endogenous metabolites showed dysregulation in serum, and 51 did so in urine. Four shared differential metabolites—glycoursodeoxycholic acid, urobilin, glycocholic acid, and urobilinogen—were identified in both biofluids. Pathway enrichment analysis revealed three co - regulated metabolic pathways: tryptophan metabolism, glycerophospholipid metabolism, and porphyrin metabolism (p < 0.05).

This study delineates the distinct metabolic signatures of cirrhosis and proposes a diagnostic strategy based on dual - biofluid analysis. The intersectional biomarkers and pathways elucidate the mechanisms linking bile acid homeostasis and hemoprotein catabolism to cirrhotic progression, offering a noninvasive approach for clinical detection.

## Linked entities

- **Chemicals:** glycoursodeoxycholic acid (PubChem CID 93353), urobilin (PubChem CID 5280819), glycocholic acid (PubChem CID 10140), urobilinogen (PubChem CID 26818)

## Full-text entities

- **Genes:** TF (transferrin) [NCBI Gene 7018] {aka HEL-S-71p, PRO1557, PRO2086, TFQTL1}, PPARA (peroxisome proliferator activated receptor alpha) [NCBI Gene 5465] {aka NR1C1, PPAR, PPAR-alpha, PPARalpha, hPPAR}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, S1PR2 (sphingosine-1-phosphate receptor 2) [NCBI Gene 9294] {aka AGR16, DFNB68, EDG-5, EDG5, Gpcr13, H218}, Tdo2 (tryptophan 2,3-dioxygenase) [NCBI Gene 64206] {aka TO, Tdo}, VIP (vasoactive intestinal peptide) [NCBI Gene 7432] {aka PHM27}, YAP1 (Yes1 associated transcriptional regulator) [NCBI Gene 10413] {aka COB1, YAP, YAP-1, YAP2, YAP65, YKI}
- **Diseases:** Portal hypertension (MESH:D006975), ascites (MESH:D001201), atherosclerosis (MESH:D050197), viral hepatitis (MESH:D014777), deficiency (MESH:D007153), hypertension (MESH:D006973), cholestasis (MESH:D002779), coagulation (MESH:D001778), organic diseases (MESH:D000092124), hepatic encephalopathy (MESH:D006501), liver failure (MESH:D017093), loss of appetite (MESH:D001068), primary biliary cirrhosis (MESH:D008105), hepatocellular carcinoma (MESH:D006528), primary pulmonary hypertension (MESH:D006976), sepsis (MESH:D018805), autoimmune hepatitis (MESH:D019693), gastrointestinal bleeding (MESH:D006471), cognitive impairment (MESH:D003072), Cirrhosis (MESH:D005355), inflammation (MESH:D007249), CLDs (MESH:D008107), chronic hepatitis (MESH:D006521), alcohol misuse (MESH:D000437), cirrhotic (MESH:D000094724), pain (MESH:D010146), cancer cachexia (MESH:D009369), diabetes (MESH:D003920), non-alcoholic fatty liver disease (MESH:D065626), anorexia (MESH:D000855), Liver cirrhosis (MESH:D008103), hepatorenal syndrome (MESH:D006530), obesity (MESH:D009765), fatigue (MESH:D005221), metabolic disorders (MESH:D008659), bile duct rupture (MESH:D001649), pruritus (MESH:D011537)
- **Chemicals:** L-ornithine L-aspartate (MESH:C002939), bile acid (MESH:D001647), hypotaurine (MESH:C003949), amino sugar (MESH:D000606), porphyrin (MESH:D011166), 7alpha-hydroxy-3-oxo-4-cholestenoate (-), glucuronate (MESH:D020723), urobilin (MESH:D014557), L-aspartate (MESH:D001224), glycoursodeoxycholic acid (MESH:C024033), arginine (MESH:D001120), CoA (MESH:D003065), steroid hormone (MESH:D013256), beta-alanine (MESH:D015091), Taurine (MESH:D013654), lipid (MESH:D008055), ammonium acetate (MESH:C018824), Tryptophan (MESH:D014364), alcohol (MESH:D000438), reactive oxygen species (MESH:D017382), calcium (MESH:D002118), indole (MESH:C030374), 5-HT (MESH:D012701), proline (MESH:D011392), methanol (MESH:D000432), glycerophosphocholine (MESH:D005997), cGMP (MESH:D006152), ammonia (MESH:D000641), salt (MESH:D012492), glycerophospholipid (MESH:D020404), acid (MESH:D000143), Bilirubin (MESH:D001663), dihydrouracil (MESH:C007419), alanine (MESH:D000409), acetonitrile (MESH:C032159), urobilinogen (MESH:D014558), taurocholate (MESH:D013656), arachidonate (MESH:D016718), glycocholate (MESH:D006000), L-glutamate (MESH:D018698), Kynurenine (MESH:D007737), glycine (MESH:D005998), pentose (MESH:D010429), nitric oxide (MESH:D009569), cholesterol (MESH:D002784)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

32 references — full list in the complete paper: https://tomesphere.com/paper/PMC12926344/full.md

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Source: https://tomesphere.com/paper/PMC12926344