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Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Aug 15, 2021; 13(8): 799-821
Published online Aug 15, 2021. doi: 10.4251/wjgo.v13.i8.799
B7 homologue 3 as a prognostic biomarker and potential therapeutic target in gastrointestinal tumors
Petar Rasic, Maja Jovanovic-Tucovic, Marija Jeremic, Slavisa M Djuricic, Zorica V Vasiljevic, Maja Milickovic, Djordje Savic
Petar Rasic, Maja Milickovic, Djordje Savic, Department of Abdominal Surgery, Mother and Child Health Care Institute of Serbia “Dr. Vukan Cupic“, Belgrade 11 000, Serbia
Maja Jovanovic-Tucovic, Marija Jeremic, Institute of Medical and Clinical Biochemistry, School of Medicine, University of Belgrade, Belgrade 11 000, Serbia
Slavisa M Djuricic, Department of Clinical Pathology, Mother and Child Health Care Institute of Serbia “Dr. Vukan Cupic“, Belgrade 11 000, Serbia
Slavisa M Djuricic, Faculty of Medicine, University of Banja Luka, Banja Luka 78 000, Bosnia and Herzegovina
Zorica V Vasiljevic, Department of Clinical Microbiology, Mother and Child Health Care Institute of Serbia “Dr. Vukan Cupic“, Belgrade 11 000, Serbia
Maja Milickovic, Djordje Savic, School of Medicine, University of Belgrade, Belgrade 11 000, Serbia
Author contributions: Rasic P, Jovanovic-Tucovic M, and Jeremic M drafted the manuscript; Djuricic SM, Vasiljevic ZV, Milickovic M, and Savic D substantively revised the manuscript; all authors read and approved the final version of the manuscript.
Conflict-of-interest statement: The authors declare no conflicts of interest.
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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Petar Rasic, MD, Doctor, Department of Abdominal Surgery, Mother and Child Health Care Institute of Serbia “Dr. Vukan Cupic“, Radoja Dakica 6-8, Belgrade 11 000, Serbia. petar.rasic@imd.org.rs
Received: February 20, 2021
Peer-review started: February 20, 2021
First decision: April 6, 2021
Revised: April 19, 2021
Accepted: July 7, 2021
Article in press: July 7, 2021
Published online: August 15, 2021
Abstract

The most common digestive system (DS) cancers, including tumors of the gastrointestinal tract (GIT) such as colorectal cancer (CRC), gastric cancer (GC) and esophageal cancer (EC) as well as tumors of DS accessory organs such as pancreatic and liver cancer, are responsible for more than one-third of all cancer-related deaths worldwide, despite the progress that has been achieved in anticancer therapy. Due to these limitations in treatment strategies, oncological research has taken outstanding steps towards a better understanding of cancer cell biological complexity and heterogeneity. These studies led to new molecular target-driven therapeutic approaches. Different in vivo and in vitro studies have revealed significant expression of B7 homologue 3 (B7-H3) among the most common cancers of the GIT, including CRC, GC, and EC, whereas B7-H3 expression in normal healthy tissue of these organs was shown to be absent or minimal. This molecule is able to influence the biological behavior of GIT tumors through the various immunological and nonimmunological molecular mechanisms, and some of them are shown to be the result of B7-H3-related induction of signal transduction pathways, such as Janus kinase 2/signal transducer and activator of transcription 3, phosphatidylinositol 3-kinase/protein kinase B, extracellular signal-regulated kinase, and nuclear factor-κB. B7-H3 exerts an important role in progression, metastasis and resistance to anticancer therapy in these tumors. In addition, the results of many studies suggest that B7-H3 stimulates immune evasion in GIT tumors by suppressing antitumor immune response. Accordingly, it was observed that experimental depletion or inhibition of B7-H3 in gastrointestinal cancers improved antitumor immune response, impaired tumor progression, invasion, angiogenesis, and metastasis and decreased resistance to anticancer therapy. Finally, the high expression of B7-H3 in most common cancers of the GIT was shown to be associated with poor prognosis. In this review, we summarize the established data from different GIT cancer-related studies and suggest that the B7-H3 molecule could be a promising prognostic biomarker and therapeutic target for anticancer immunotherapy in these tumors.

Keywords: B7 homologue 3, Gastrointestinal tumors, Colorectal cancer, Gastric cancer, Esophageal cancer, Targeted therapy

Core Tip: Limitations related to oncotherapy and poor survival of patients with advanced forms of the most common malignant tumors of the gastrointestinal tract, including colorectal, gastric, and esophageal cancers (ECs), have led researchers to investigate new molecular target-driven therapeutic approaches. B7 homologue 3 (B7-H3) was shown to be significantly overexpressed among various malignancies and associated with their progression, metastasis and resistance to anticancer therapy. In this review, we analyze the results of different studies related to B7-H3 in colorectal, gastric, and ECs and suggest that this molecule could be a promising prognostic biomarker and therapeutic target in these tumors.