# Lipidomic analysis of bile from patients with extrahepatic cholangiocarcinoma

**Authors:** Seong Ji Choi, Hyo Jung Kim, Sung Won Kwon, Won Shik Kim, Jae Seon Kim, Kishor Pant, Kishor Pant, Robin Clugston

PMC · DOI: 10.1371/journal.pone.0345136 · PLOS One · 2026-03-19

## TL;DR

This study compares bile lipid profiles in patients with cholangiocarcinoma, gallstones, and healthy individuals to identify potential biomarkers for these conditions.

## Contribution

The study reveals distinct lipidomic patterns in bile that differentiate extrahepatic cholangiocarcinoma and choledocholithiasis from healthy controls.

## Key findings

- Phosphatidylcholine levels were lower in both eCCA and choledocholithiasis compared to controls.
- Diacylglycerol lipids were higher in eCCA, while acylcarnitine lipids were higher in choledocholithiasis.
- Lysophosphatidylcholine levels were significantly lower in eCCA than in choledocholithiasis.

## Abstract

Cholangiocarcinoma and gallstones are significant gastrointestinal diseases with diverse etiologies and complex clinical manifestations. Understanding their underlying molecular mechanisms is crucial for advancing diagnosis and treatment strategies. In this study, we compared the lipidomic profiles of bile samples from patients with extrahepatic cholangiocarcinoma (eCCA) or choledocholithiasis with those of healthy controls to identify potential biomarkers and therapeutic targets.

Bile samples were prospectively collected from 33 patients undergoing endoscopic retrograde cholangiopancreatography at the Korea University Guro Hospital, including 12 patients with eCCA, 15 with choledocholithiasis, and six controls. Lipidomic profiling was performed using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry. Principal component analysis, ANOVA, and volcano plots were used to identify the differential lipidomic signatures across the groups.

A total of 230 lipid metabolites were identified, and significant differences were observed among the groups; each group had distinct lipidomic patterns. In both eCCA and choledocholithiasis, phosphatidylcholine contents were consistently more downregulated than in controls. However, diacylglycerol lipids were upregulated in eCCA while acylcarnitine lipids were upregulated in choledocholithiasis. Lysophosphatidylcholine levels were notably lower in patients with eCCA than in those with choledocholithiasis.

Our results suggested that specific lipidomic changes and their inter-relationships contribute to the pathophysiology of choledocholithiasis and eCCA. Longitudinal studies and functional assays can further validate the findings and translate them into clinical practice.

## Linked entities

- **Diseases:** cholangiocarcinoma (MONDO:0019087), choledocholithiasis (MONDO:0006699)

## Full-text entities

- **Genes:** TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, PCSK7 (proprotein convertase subtilisin/kexin type 7) [NCBI Gene 9159] {aka LPC, PC7, PC8, SPC7}, ATHS (atherosclerosis susceptibility (lipoprotein associated)) [NCBI Gene 470] {aka ALP}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CXADRP1 (CXADR pseudogene 1) [NCBI Gene 653108] {aka CAR, CXADRP}, mucin [NCBI Gene 100508689], MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}, ABCB4 (ATP binding cassette subfamily B member 4) [NCBI Gene 5244] {aka ABC21, GBD1, ICP3, MDR2, MDR2/3, MDR3}, SLC17A5 (solute carrier family 17 member 5) [NCBI Gene 26503] {aka AST, ISSD, NSD, SD, SIALIN, SIASD}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, PC (pyruvate carboxylase) [NCBI Gene 5091] {aka PCB}, PLA2G1B (phospholipase A2 group IB) [NCBI Gene 5319] {aka PLA2, PLA2A, PPLA2}, Pcx (pyruvate carboxylase) [NCBI Gene 18563] {aka Pc, Pcb}, DGKA (diacylglycerol kinase alpha) [NCBI Gene 1606] {aka DAGK, DAGK1, DGK-alpha}, Abcb4 (ATP-binding cassette, sub-family B member 4) [NCBI Gene 18670] {aka Mdr2, Pgy-2, Pgy2, mdr-2}, PRRT2 (proline rich transmembrane protein 2) [NCBI Gene 112476] {aka BFIC2, BFIS2, DSPB3, DYT10, EKD1, FICCA}
- **Diseases:** glioblastoma (MESH:D005909), cholangitis (MESH:D002761), carcinogenesis (MESH:D063646), cancer (MESH:D009369), bile duct cancer (MESH:D001650), CCA (MESH:D018281), Gallstones (MESH:D042882), PC (MESH:C535298), biliary tract cancer (MESH:D001661), metabolic dysfunction (MESH:D008659), ductal obstruction (MESH:D044584), abdominal pain (MESH:D015746), infection (MESH:D007239), gastrointestinal diseases (MESH:D005767), benign biliary injury (MESH:D001658), gallstone disease (MESH:D002769), biliary disease (MESH:D001660), bile (MESH:D001649), biliary inflammation (MESH:D007249), lipid abnormalities (MESH:D011017), fever (MESH:D005334), cytotoxic (MESH:D064420), stone formation (MESH:D058426), damage (MESH:D020263), cholesterol stones (MESH:D007669), bile duct obstruction (MESH:D002779), tumorigenic (MESH:D002471), bile acid abnormalities (MESH:C567652), choledocholithiasis (MESH:D042883), ORCID iD (MESH:C535742)
- **Chemicals:** salt (MESH:D012492), fatty acid (MESH:D005227), methanol (MESH:D000432), Lysophosphatidylcholine (MESH:D008244), bilirubin (MESH:D001663), DG (MESH:D004075), bile acid (MESH:D001647), phospholipid (MESH:D010743), Toluene (MESH:D014050), MG (MESH:D008274), acetonitrile (MESH:C032159), calcium (MESH:D002118), Cer (MESH:D002518), PE (MESH:D010714), cholesterol (MESH:D002784), ROS (MESH:D017382), LPCs (-), PC (MESH:D010713), water (MESH:D014867), 2-propanol (MESH:D019840), Lipid (MESH:D008055), ACN (MESH:C084683), ammonium formate (MESH:C030544), MTBE (MESH:C043243), lecithin (MESH:D054709), palmitate (MESH:D010168), acylcarnitine (MESH:C116917)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13001927/full.md

## References

22 references — full list in the complete paper: https://tomesphere.com/paper/PMC13001927/full.md

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Source: https://tomesphere.com/paper/PMC13001927