Urine proteomics study reveals potential biomarkers for the differential diagnosis of cholangiocarcinoma and periductal fibrosis

• Published in: PloS one 2019-08, Vol.14 (8), p.e0221024-e0221024
• Main Authors: Duangkumpha, Kassaporn, Stoll, Thomas, Phetcharaburanin, Jutarop, Yongvanit, Puangrat, Thanan, Raynoo, Techasen, Anchalee, Namwat, Nisana, Khuntikeo, Narong, Chamadol, Nittaya, Roytrakul, Sittiruk, Mulvenna, Jason, Mohamed, Ahmed, Shah, Alok K, Hill, Michelle M, Loilome, Watcharin
• Format: Article
• Language: English
• Subjects: Adult; Aged; Animals; Autophagy; Bile Duct Neoplasms - diagnosis; Bile Duct Neoplasms - pathology; Bile Duct Neoplasms - urine; Bile ducts; Bile Ducts - pathology; Biliary tract cancer; Biochemistry; Bioinformatics; Biological markers; Biology and Life Sciences; Biomarkers; Biomarkers, Tumor - urine; Biosynthesis; Cadherins; Cancer; Cancer research; Cholangiocarcinoma; Cholangiocarcinoma - diagnosis; Cholangiocarcinoma - pathology; Cholangiocarcinoma - urine; Colon; Containers; Depletion; Diagnosis; Diagnosis, Differential; Differential diagnosis; Discriminant analysis; Female; Fibrosis; Gene expression; Glycoproteins; Humans; Immunohistochemistry; Infection; Infections; Literature reviews; Liver cancer; Male; Mass spectrometry; Mass spectroscopy; Medical diagnosis; Medical prognosis; Medical research; Medicine; Medicine and Health Sciences; Methods; Middle Aged; Monitoring; Opisthorchiasis - complications; People and Places; Peptides; Physical Sciences; Precancerous Conditions - diagnosis; Precancerous Conditions - etiology; Precancerous Conditions - pathology; Precancerous Conditions - urine; Proteins; Proteomics; Proteomics - methods; Research and Analysis Methods; Spectroscopy; Tandem Mass Spectrometry - methods; Thailand; Tumors; Ultrasonic imaging; Ultrasonography; Ultrasound; Ultrasound imaging; Urinalysis; Urine
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0221024

Cholangiocarcinoma (CCA) is a primary malignant tumor of the epithelial lining of biliary track associated with endemic Opisthorchis viverrini (Ov) infection in northeastern Thailand. Ov-associated periductal fibrosis (PDF) is the precancerous lesion for CCA, and can be detected by ultrasonography (US) to facilitate early detection. However, US cannot be used to distinguish PDF from cancer. Therefore, the objective of this study was to discover and qualify potential urine biomarkers for CCA detection in at-risk population. Biomarker discovery was conducted on pooled urine samples, 42 patients per group, with PDF or normal bile duct confirmed by ultrasound. After depletion of high abundance proteins, 338 urinary proteins were identified from the 3 samples (normal-US, PDF-US, CCA). Based on fold change and literature review, 70 candidate proteins were selected for qualification by multiple reaction monitoring mass spectrometry (MRM-MS) in 90 individual urine samples, 30 per group. An orthogonal signal correction projection to latent structures discriminant analysis (O-PLS-DA) multivariate model constructed from the 70 candidate biomarkers significantly discriminated CCA from normal and PDF groups (P = 0.003). As an independent validation, the expression of 3 candidate proteins was confirmed by immunohistochemistry in CCA tissues: Lysosome associated membrane glycoprotein 1 (LAMP1), lysosome associated membrane glycoprotein 2 (LAMP2) and cadherin-related family member 2 (CDHR2). Further evaluation of these candidate biomarkers in a larger cohort is needed to support their applicability in a clinical setting for screening and monitoring early CCA and for CCA surveillance.