J Gastric Cancer.  2023 Apr;23(2):340-354. 10.5230/jgc.2023.23.e19.

Fatty Acid Binding Protein 5 (FABP5) Promotes Aggressiveness of Gastric Cancer Through Modulation of Tumor Immunity

• Qiu Mq
• Wang Hj
• Ju Yf
• Sun L
• Liu Z
• Wang T
• Kan Sf
• Yang Z
• Cui Yy
• Ke Yq
• He Hm
• Zhang S

• KMID: 2547749
• DOI: http://doi.org/10.5230/jgc.2023.23.e19

Abstract

Purpose
Gastric cancer (GC) is the second most lethal cancer globally and is associated with poor prognosis. Fatty acid-binding proteins (FABPs) can regulate biological properties of carcinoma cells. FABP5 is overexpressed in many types of cancers; however, the role and mechanisms of action of FABP5 in GC remain unclear. In this study, we aimed to evaluate the clinical and biological functions of FABP5 in GC.
Materials and Methods
We assessed FABP5 expression using immunohistochemical analysis in 79 patients with GC and evaluated its biological functions following in vitro and in vivo ectopic expression. FABP5 targets relevant to GC progression were determined using RNA sequencing (RNA-seq).
Results
Elevated FABP5 expression was closely associated with poor outcomes, and ectopic expression of FABP5 promoted proliferation, invasion, migration, and carcinogenicity of GC cells, thus suggesting its potential tumor-promoting role in GC. Additionally, RNA-seq analysis indicated that FABP5 activates immune-related pathways, including cytokinecytokine receptor interaction pathways, interleukin-17 signaling, and tumor necrosis factor signaling, suggesting an important rationale for the possible development of therapies that combine FABP5-targeted drugs with immunotherapeutics.
Conclusions
These findings highlight the biological mechanisms and clinical implications of FABP5 in GC and suggest its potential as an adverse prognostic factor and/or therapeutic target.

Keyword

Fatty acid binding protein 5; Gastric cancer; Biomarker; Interleukin-17