Qiu Mei-Qing, Wang Hui-Jun, Ju Ya-Fei, Sun Li, Liu Zhen, Wang Tao, Kan Shi-Feng, Yang Zhen, Cui Ya-Yun, Ke You-Qiang, He Hong-Min, Zhang Shu
Shandong University Cancer Center, Jinan, China.
Department of Gastroenterology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
J Gastric Cancer. 2023 Apr;23(2):340-354. doi: 10.5230/jgc.2023.23.e19.
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.
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).
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.
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.
胃癌（GC）是全球第二大致命性癌症，且预后较差。脂肪酸结合蛋白（FABP）可调节癌细胞的生物学特性。FABP5在多种癌症中均有过表达；然而，FABP5在胃癌中的作用及作用机制仍不清楚。在本研究中，我们旨在评估FABP5在胃癌中的临床及生物学功能。
我们采用免疫组织化学分析评估了79例胃癌患者的FABP5表达情况，并在体外和体内异位表达后评估了其生物学功能。使用RNA测序（RNA-seq）确定与胃癌进展相关的FABP5靶点。
FABP5表达升高与不良预后密切相关，FABP5的异位表达促进了胃癌细胞的增殖、侵袭、迁移及致癌性，从而表明其在胃癌中具有潜在的促肿瘤作用。此外，RNA-seq分析表明，FABP5激活免疫相关通路，包括细胞因子-细胞因子受体相互作用通路、白细胞介素-17信号通路和肿瘤坏死因子信号通路，这为将FABP5靶向药物与免疫治疗相结合的疗法的可能开发提供了重要依据。
这些发现突出了FABP5在胃癌中的生物学机制及临床意义，并表明其作为不良预后因素和/或治疗靶点的潜力。
