Review
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 21, 2022; 28(15): 1508-1525
Published online Apr 21, 2022. doi: 10.3748/wjg.v28.i15.1508
Novel approaches in search for biomarkers of cholangiocarcinoma
Lavinia-Patricia Mocan, Maria Ilieș, Carmen Stanca Melincovici, Mihaela Spârchez, Rareș Crăciun, Iuliana Nenu, Adelina Horhat, Cristian Tefas, Zeno Spârchez, Cristina Adela Iuga, Tudor Mocan, Carmen Mihaela Mihu
Lavinia-Patricia Mocan, Carmen Stanca Melincovici, Carmen Mihaela Mihu, Department of Histology, Faculty of Medicine, "Iuliu Hațieganu" University of Medicine and Pharmacy, Cluj-Napoca 400012, Romania
Maria Ilieș, Cristina Adela Iuga, Department of Proteomics and Metabolomics, MedFUTURE Research Center for Advanced Medicine, "Iuliu Hațieganu" University of Medicine and Pharmacy, Cluj-Napoca 400349, Romania
Mihaela Spârchez, 2nd Pediatrics Department, Faculty of Medicine, "Iuliu Hațieganu" University of Medicine and Pharmacy, Cluj-Napoca 400012, Romania
Rareș Crăciun, Iuliana Nenu, Adelina Horhat, Cristian Tefas, Zeno Spârchez, Tudor Mocan, 3rd Medical Department, Faculty of Medicine, "Iuliu Hațieganu" University of Medicine and Pharmacy, Cluj-Napoca 400012, Romania
Rareș Crăciun, Iuliana Nenu, Adelina Horhat, Cristian Tefas, Zeno Spârchez, Tudor Mocan, Department of Gastroenterology, "Prof. dr. Octavian Fodor" Institute for Gastroenterology and Hepatology, Cluj-Napoca 400162, Romania
Cristina Adela Iuga, Department of Pharmaceutical Analysis, Faculty of Pharmacy, "Iuliu Hațieganu" University of Medicine and Pharmacy, Cluj-Napoca 400012, Romania
Author contributions: Ilieș M, Mocan T, Mihu CM made the conception and design; Mocan LP, Crăciun R, Nenu I, Horhat A, Spârchez M, Melincovici CS, Ilieș M, Mocan T made the acquisition, analysis, and interpretation of data; Spârchez Z, Ilieș M, Iuga CA, Mocan T and Mihu CM performed critical revisions of the manuscript; all authors contributed their expert opinion to the concept of the paper, critically revised the article, and approved the final article version to be published.
Supported by The Romanian National Ministry of Research, Innovation and Digitalization, CNCS-UEFISCDI: Postdoctoral Research Project PN-III-P1-1.1-PD-2019-0852/PD113 within PNCDI III, awarded to Maria Ilieș.
Conflict-of-interest statement: All authors have no conflict of interest to declare.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Maria Ilieș, PhD, Academic Research, Department of Proteomics and Metabolomics, MedFUTURE Research Center for Advanced Medicine, "Iuliu Hațieganu" University of Medicine and Pharmacy, Marinescu 23, Cluj-Napoca 400349, Romania. ilies.maria@umfcluj.ro
Received: October 31, 2021
Peer-review started: October 31, 2021
First decision: November 29, 2021
Revised: December 12, 2021
Accepted: March 6, 2022
Article in press: March 6, 2022
Published online: April 21, 2022
Processing time: 165 Days and 22.9 Hours
Abstract

Cholangiocarcinoma (CCA) arises from the ductular epithelium of the biliary tree, either within the liver (intrahepatic CCA) or more commonly from the extrahepatic bile ducts (extrahepatic CCA). This disease has a poor prognosis and a growing worldwide prevalence. The poor outcomes of CCA are partially explained by the fact that a final diagnosis is challenging, especially the differential diagnosis between hepatocellular carcinoma and intrahepatic CCA, or distal CCA and pancreatic head adenocarcinoma. Most patients present with an advanced disease, unresectable disease, and there is a lack in non-surgical therapeutic modalities. Not least, there is an acute lack of prognostic biomarkers which further complicates disease management. Therefore, there is a dire need to find alternative diagnostic and follow-up pathways that can lead to an accurate result, either singlehandedly or combined with other methods. In the "-omics" era, this goal can be attained by various means, as it has been successfully demonstrated in other primary tumors. Numerous variants can reach a biomarker status ranging from circulating nucleic acids to proteins, metabolites, extracellular vesicles, and ultimately circulating tumor cells. However, given the relatively heterogeneous data, extracting clinical meaning from the inconsequential noise might become a tall task. The current review aims to navigate the nascent waters of the non-invasive approach to CCA and provide an evidence-based input to aid clinical decisions and provide grounds for future research.

Keywords: Cholangiocarcinoma; Biomarker; Proteomics; Metabolomics; Extracellular vesicles; Circulating nucleic acids

Core Tip: The current review paper aims to critically analyze the most recent developments in non-invasive cholangiocarcinoma diagnosis and prognosis. The article takes an in-depth look at the fields of circulating nucleic acids, proteomic and metabolomic-derived biomarkers, extracellular vesicles, and circulating tumor cells in an attempt to outline promising results for future research and clinical use.