Dataset Information

Pilot Multi-Omic Analysis of Human Bile from Benign and Malignant Biliary Strictures: A Machine-Learning Approach.

ABSTRACT: Cholangiocarcinoma (CCA) and pancreatic adenocarcinoma (PDAC) may lead to the development of extrahepatic obstructive cholestasis. However, biliary stenoses can also be caused by benign conditions, and the identification of their etiology still remains a clinical challenge. We performed metabolomic and proteomic analyses of bile from patients with benign (n = 36) and malignant conditions, CCA (n = 36) or PDAC (n = 57), undergoing endoscopic retrograde cholangiopancreatography with the aim of characterizing bile composition in biliopancreatic disease and identifying biomarkers for the differential diagnosis of biliary strictures. Comprehensive analyses of lipids, bile acids and small molecules were carried out using mass spectrometry (MS) and nuclear magnetic resonance spectroscopy (1H-NMR) in all patients. MS analysis of bile proteome was performed in five patients per group. We implemented artificial intelligence tools for the selection of biomarkers and algorithms with predictive capacity. Our machine-learning pipeline included the generation of synthetic data with properties of real data, the selection of potential biomarkers (metabolites or proteins) and their analysis with neural networks (NN). Selected biomarkers were then validated with real data. We identified panels of lipids (n = 10) and proteins (n = 5) that when analyzed with NN algorithms discriminated between patients with and without cancer with an unprecedented accuracy.

SUBMITTER: Urman JM

PROVIDER: S-EPMC7352944 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

Pilot Multi-Omic Analysis of Human Bile from Benign and Malignant Biliary Strictures: A Machine-Learning Approach.

Urman Jesús M JM Herranz José M JM Uriarte Iker I Rullán María M Oyón Daniel D González Belén B Fernandez-Urién Ignacio I Carrascosa Juan J Bolado Federico F Zabalza Lucía L Arechederra María M Alvarez-Sola Gloria G Colyn Leticia L Latasa María U MU Puchades-Carrasco Leonor L Pineda-Lucena Antonio A Iraburu María J MJ Iruarrizaga-Lejarreta Marta M Alonso Cristina C Sangro Bruno B Purroy Ana A Gil Isabel I Carmona Lorena L Cubero Francisco Javier FJ Martínez-Chantar María L ML Banales Jesús M JM Romero Marta R MR Macias Rocio I R RIR Monte Maria J MJ Marín Jose J G JJG Vila Juan J JJ Corrales Fernando J FJ Berasain Carmen C Fernández-Barrena Maite G MG Avila Matías A MA

Cancers 20200621 6

Cholangiocarcinoma (CCA) and pancreatic adenocarcinoma (PDAC) may lead to the development of extrahepatic obstructive cholestasis. However, biliary stenoses can also be caused by benign conditions, and the identification of their etiology still remains a clinical challenge. We performed metabolomic and proteomic analyses of bile from patients with benign (n = 36) and malignant conditions, CCA (n = 36) or PDAC (n = 57), undergoing endoscopic retrograde cholangiopancreatograph ...[more]

PMID: 32575903

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Project description:Patients with cholangiocarcinoma have poor survival since the majority of patients are diagnosed at a stage precluding surgical resection, due to locally irresectable tumors and/or metastases. Optimization of diagnostic strategies, with a principal role for tissue diagnosis, is essential to detect cancers at an earlier stage amenable to curative treatment. Current barriers for a tissue diagnosis include both insufficient tissue sampling and a difficult cyto- or histopathological assessment. During endoscopic retrograde cholangiopancreatography, optimal brush sampling includes obtaining more than one brush within an individual patient to increase its diagnostic value. Currently, no significant increase of the diagnostic accuracy for the new cytology brush devices aiming to enhance the cellularity of brushings versus standard biliary brush devices has been demonstrated. Peroral cholangioscopy with bile duct biopsies appears to be a valuable tool in the diagnostic work-up of indeterminate biliary strictures, and may overcome current technical difficulties of fluoroscopic-guided biopsies. Over the past years, molecular techniques to detect chromosomal instability, mutations and methylation profiling of tumors have revolutionized, and implementation of these techniques on biliary tissue during diagnostic work-up of biliary strictures may be awaited in the near future. Fluorescence in situ hybridization has already been implemented in routine diagnostic evaluation of biliary strictures in several centers. Next-generation sequencing is promising for standard diagnostic care in biliary strictures, and recent studies have shown adequate detection of prevalent genomic alterations in KRAS, TP53, CDKN2A, SMAD4, PIK3CA, and GNAS on biliary brush material. Detection of DNA methylation of tumor suppressor genes and microRNAs may evolve over the coming years to a valuable diagnostic tool for cholangiocarcinoma. This review summarizes optimal strategies for biliary tissue sampling during endoscopic retrograde cholangiopancreatography and focuses on the evolving molecular techniques on biliary tissue to improve the differentiation of benign and malignant biliary strictures.

Dataset Information

Pilot Multi-Omic Analysis of Human Bile from Benign and Malignant Biliary Strictures: A Machine-Learning Approach.

Publications

Pilot Multi-Omic Analysis of Human Bile from Benign and Malignant Biliary Strictures: A Machine-Learning Approach.

Similar Datasets

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