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Usefulness of bile as a biomarker via ferroptosis and cysteine prenylation in cholangiocarcinoma; role of diagnosis and differentiation from benign biliary disease
- Source :
- Surgical Oncology. 34:174-181
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Background Cholangiocarcinoma (CCA) is a malignant cancer of the biliary tract with a poor prognosis. Herein, we investigated possible mechanism of extrahepatic CCA (eCCA) by dysregulated iron metabolism and post-translational modifications (PTMs). Further, we evaluated potential biomarkers in the bile fluid for diagnosis of eCCA and differentiation between eCCA and benign biliary disease. Methods From August 2018 to April 2019, we obtained bile fluids from 46 patients; 28 patients with eCCA (eCCA group) and 18 patients with common bile duct stone (Control group) via percutaneous transhepatic biliary drainage. We examined the levels of reduced glutathione (GSH), peroxide, ferrous iron [Fe+2], glutathione peroxidase (GPX) and farnesyl transferase/geranylgeranyl transferase type-1 subunit alpha (FNTA) concentration in bile fluids to clarify the mechanism of ferroptosis and prenylation. Results The remarkable difference of PTMs was that FNTA which means prenylated cysteine as regulator was significantly decreased in eCCA than that of control. In addition, level of GSH, peroxide, GPX and ferrous iron [Fe+2] were significantly depleted in eCCA than control. These results demonstrate that PTM, dysregulated iron metabolism and GPX-regulated ferroptosis with GSH depletion through cysteine modification in bile are possible mechanisms of eCCA. Liquid Chromatography (LC)-Mass Spectrometry (MS) analysis, several oncogenic pathways including MYC target, apoptosis, fatty acid metabolism, P53 and mTORC1 were enriched in eCCA. Conclusions In conclusion, redox-dependent modification of cysteine and ferroptosis in bile fluids are possible mechanisms of eCCA. Several protein and oncogenic pathways related to PTM which are seen in eCCA tissues were also enriched in bile fluids. It suggests that bile fluid represents the oncogenic characteristics of eCCA tissues. Therefore, bile fluids have a role of a biomarker for diagnosis in eCCA, especially, differentiation of eCCA from benign biliary stricture.
- Subjects :
- Male
0301 basic medicine
Constriction, Pathologic
Cholangiocarcinoma
Diagnosis, Differential
Biliary disease
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Prenylation
Biomarkers, Tumor
medicine
Bile
Ferroptosis
Humans
Cysteine
Aged
chemistry.chemical_classification
Fatty acid metabolism
business.industry
Glutathione peroxidase
Glutathione
Prognosis
medicine.disease
Bile Ducts, Intrahepatic
030104 developmental biology
Bile Duct Neoplasms
Oncology
chemistry
Apoptosis
Biliary tract
Case-Control Studies
030220 oncology & carcinogenesis
Cancer research
Female
Surgery
business
Follow-Up Studies
Subjects
Details
- ISSN :
- 09607404
- Volume :
- 34
- Database :
- OpenAIRE
- Journal :
- Surgical Oncology
- Accession number :
- edsair.doi.dedup.....11693684d834cf09027c2709d3a32430