Review
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 28, 2024; 30(12): 1680-1705
Published online Mar 28, 2024. doi: 10.3748/wjg.v30.i12.1680
Liquid biopsy for gastric cancer: Techniques, applications, and future directions
Cristina Díaz del Arco, M Jesús Fernández Aceñero, Luis Ortega Medina
Cristina Díaz del Arco, M Jesús Fernández Aceñero, Luis Ortega Medina, Department of Surgical Pathology, Health Research Institute of the Hospital Clínico San Carlos, Hospital Clínico San Carlos, Madrid 28040, Spain
Cristina Díaz del Arco, M Jesús Fernández Aceñero, Luis Ortega Medina, Department of Legal Medicine, Psychiatry and Pathology, Universidad Complutense de Madrid, Madrid 28040, Spain
Author contributions: Díaz del Arco C participated in the data acquisition, interpretation, manuscript draft, approval, and agreement; Fernández Aceñero MJ participated in the study design, data acquisition, manuscript revision, approval, and agreement; and Ortega Medina L participated in the study design, data acquisition, manuscript revision, approval, and agreement.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
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: Cristina Díaz del Arco, MD, PhD, Associate Professor, Staff Physician, Department of Surgical Pathology, Health Research Institute of the Hospital Clínico San Carlos, Hospital Clínico San Carlos, c/Profesor Martín Lagos s/n, Madrid 28040, Spain. crisdelarco@gmail.com
Received: December 4, 2023
Peer-review started: December 4, 2023
First decision: January 23, 2024
Revised: February 1, 2024
Accepted: March 8, 2024
Article in press: March 8, 2024
Published online: March 28, 2024
Processing time: 114 Days and 16.6 Hours
Abstract

After the study of circulating tumor cells in blood through liquid biopsy (LB), this technique has evolved to encompass the analysis of multiple materials originating from the tumor, such as nucleic acids, extracellular vesicles, tumor-educated platelets, and other metabolites. Additionally, research has extended to include the examination of samples other than blood or plasma, such as saliva, gastric juice, urine, or stool. LB techniques are diverse, intricate, and variable. They must be highly sensitive, and pre-analytical, patient, and tumor-related factors significantly influence the detection threshold, diagnostic method selection, and potential results. Consequently, the implementation of LB in clinical practice still faces several challenges. The potential applications of LB range from early cancer detection to guiding targeted therapy or immunotherapy in both early and advanced cancer cases, monitoring treatment response, early identification of relapses, or assessing patient risk. On the other hand, gastric cancer (GC) is a disease often diagnosed at advanced stages. Despite recent advances in molecular understanding, the currently available treatment options have not substantially improved the prognosis for many of these patients. The application of LB in GC could be highly valuable as a non-invasive method for early diagnosis and for enhancing the management and outcomes of these patients. In this comprehensive review, from a pathologist’s perspective, we provide an overview of the main options available in LB, delve into the fundamental principles of the most studied techniques, explore the potential utility of LB application in the context of GC, and address the obstacles that need to be overcome in the future to make this innovative technique a game-changer in cancer diagnosis and treatment within clinical practice.

Keywords: Liquid biopsy; Gastric cancer; Circulating tumor cells; Cell-free DNA; Circulating tumor DNA; Molecular

Core Tip: Liquid biopsy (LB) has the potential to revolutionize cancer diagnostics, offering reduced invasiveness and improved understanding of tumor heterogeneity. Going beyond examining circulating tumor cells and cell-free DNA in blood, LB studies now explore a variety of structures and non-blood samples. Despite advancements in LB for tumor detection, prognostic assessment and treatment guidance, challenges remain, including complex and expensive techniques, lack of standardization, and suboptimal scientific evidence. In the context of gastric cancer, LB represents a promising approach, especially in advanced stages. This review navigates through LB intricacies, emphasizing its benefits while urging for future improvements to achieve clinical impact.