Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Jan 24, 2024; 15(1): 130-144
Published online Jan 24, 2024. doi: 10.5306/wjco.v15.i1.130
Fatty acid binding protein 5 is a novel therapeutic target for hepatocellular carcinoma
Yan Li, William Lee, Zhen-Gang Zhao, Yi Liu, Hao Cui, Hao-Yu Wang
Yan Li, Zhen-Gang Zhao, Yi Liu, Hao Cui, Hao-Yu Wang, Department of Gastroenterology, Tianjin Third Central Hospital, Tianjin 300170, China
William Lee, Biomedical Engineering, Texas A&M University, College Station, TX 77843, United States
Co-first authors: Yan Li and William Lee.
Author contributions: Li Y conceived and designed the study; Li Y, Lee W, Zhao ZG, Liu Y, Cui H, and Wang HY performed the experiments and analyzed the data; Li Y, Lee W, Zhao ZG, Liu Y, Cui H, and Wang HY interpreted the data; Li Y and Lee W drafted the manuscript; Liu Y, Cui H, and Wang HY revised the manuscript; All authors approved the final version of the article. Lee W contributed primarily to the bioinformatics analysis and therefore Lee W and Li Y contributed equally to the study. Li Y conceived and designed the study, performed the experiments, analyzed and interpreted the data, drafted and revised the manuscript. Lee W contributed to the bioinformatics analysis, data analysis and interpretation, as well as manuscript drafting and revision. Both authors have made substantial contributions to the study and are therefore qualified as co-first authors of the paper.
Supported by Tianjin Key Medical Discipline Construction Project, No. TJYXZDXK-034A.
Institutional review board statement: This study was approved by the Institutional Review Board (IRB) of Tianjin Third Central Hospital.
Conflict-of-interest statement: All authors have seen and agreed with the contents of the manuscript and there is no conflict of interest to declare.
Data sharing statement: For this bioinformatics analysis, we acquired the TCGA data and LIHC data as well as the data for other cancer patients from cBioPortal ( The bioinformatic platform GEPIA2 also used the TCGA datasets for the built-in analysis. No additional data are available.
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:
Corresponding author: Yan Li and William Lee, MD, Chief Physician, Department of Gastroenterology, Tianjin Third Central Hospital, No. 83 Jintang Road, Hedong District, Tianjin 300170, China.
Received: August 30, 2023
Peer-review started: August 30, 2023
First decision: November 20, 2023
Revised: December 2, 2023
Accepted: December 25, 2023
Article in press: December 25, 2023
Published online: January 24, 2024
Research background

FABP5 amplification can serve as a prognosis biomarker for the prediction of patient outcome and as a novel therapeutic target for treating hepatocellular carcinoma (HCC) with FABP5 amplification.

Research motivation

FABP5 is frequently amplified in cancer, especially in HCC, which leads to its abnormal expression in HCC. High FABP5 expression correlates well with worse patient outcome, enriched cancer hallmarks and oncogenes in HCC. Targeting FABP5 by SBFI-26 is more effective in FABP5-high expressing cells (Huh7) than FABP5-low expressing cells (HepG2).

Research objectives

FABP4, FABP5, FABP8, FABP9 and FABP12 as a gene cluster is frequently amplified in cancer, which is the most common genetic alteration for FABPs. FABP5 is highly overexpressed in cancer and its expression correlates well with worse patient outcomes. FABP5 expression highly correlates with enrichment of G2M checkpoint, TP53 signaling pathway, and many genes in the gene sets such as CDK1, CDK4, and TP53. Furthermore, FABP5 also correlates well with two co-expressed oncogenes PLK1 and BIRC5 in liver hepatocellular carcinoma (LIHC) patients. FABP5-high expressing Huh7 cells also expressed higher protein levels of p53, BIRC5, CDK1, CDK2, and CDK4 than FABP5-low expressing HepG2 cells. Huh7 is more sensitive to FABP5 inhibition than HepG2 cells.

Research methods

In this study, we accessed the public available portal of The Cancer Genome Atlas datasets of pan cancer and liver hepatocellular carcinoma LIHC by using cBioPortal and GEPIA2 portal. Based on mutation and CNA (copy number variation) datasets, we investigated genetic alterations of FABP family members in various cancer types. Based on mRNA datasets, we investigated FABP expression and their correlation with patient clinical outcome, enriched cancer hallmarks and oncogenes. For validation, we determined the protein levels of FABP5 and its correlated genes in Huh7 and HepG2 and evaluated the potential of targeting FABP5 in treating HCC.

Research results

The present study aimed to understand the genetic alterations and expression of FABP family members and their associated cancer hallmarks and oncogenes in contributing to cancer malignancies, especially HCC.

Research conclusions

Several family members including FABP4, FABP5, and FABP7 are abnormally expressed in cancer cells beyond tissue expression restriction and play important roles in cancer malignancy and progression. However, the mechanism leading to their abnormal expression is not clear.

Research perspectives

Reprogrammed lipid metabolism plays crucial roles in cell survival, growth, and evolution in many cancer types including HCC, an aggressive subtype of liver cancer. Fatty acid binding protein (FABP) family members including FABP5 play important roles in contribution to cancer progression and metastasis; however, how these FABP members, especially FABP5, are dysregulated in HCC and their contribution to HCC cancer progression have not been well defined.