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

  • Mei-qing Qiu (Shandong University Cancer Center) ;
  • Hui-jun Wang (Department of Gastroenterology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences) ;
  • Ya-fei Ju (Department of Gastroenterology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences) ;
  • Li Sun (Department of Gastroenterology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences) ;
  • Zhen Liu (Department of Gastroenterology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences) ;
  • Tao Wang (Department of Oncology, Zaozhuang Cancer Hospital) ;
  • Shi-feng Kan (Department of Oncology, Zaozhuang Municipal Hospital) ;
  • Zhen Yang (Department of Oncology, Zaozhuang Municipal Hospital) ;
  • Ya-yun Cui (Department of Gastroenterology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences) ;
  • You-qiang Ke (Molecular Pathology Laboratory, Department of Molecular and Clinical Cancer Medicine, Liverpool University) ;
  • Hong-min He (Department of Oncology, Zaozhuang Municipal Hospital) ;
  • Shu Zhang (Shandong University Cancer Center)
  • Received : 2023.04.01
  • Accepted : 2022.06.28
  • Published : 2023.04.30

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 cytokine-cytokine 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.

Keywords

References

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