Retinol Binding Protein 4 Serves as a Potential Tumor Biomarker and Promotes Malignant Behavior in Gastric Cancer

IF 2.5 4区医学 Q3 ONCOLOGY

Cancer Management and Research Pub Date : 2024-07-24 DOI:10.2147/cmar.s480337

Yantao Yu, Chenkai Zhang, Qiannan Sun, Shantanu Baral, Jianyue Ding, Fanyu Zhao, Qing Yao, Shuyang Gao, Bin Liu, Daorong Wang

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引用次数: 0

Abstract

Background: Gastric cancer (GC) is a highly phenotypically heterogeneous disease and is caused by a combination of factors. Retinol binding protein 4 (RBP4) is a member of a family of lipid transport proteins that are involved in the transport of substances between cells and play a crucial role in a variety of cancers. However, the expression and role of RBP4 in GC remain unknown.
Methods: In this study, we explored the expression, prognostic significance, immune microenvironment, drug responsiveness and function of associated signaling pathways of RBP4 in GC using web-based bioinformatics tools. Immunohistochemistry and real-time quantitative PCR were utilized to analyze the tissue and cell expression levels of RBP4. CCK-8, colony formation, EDU incorporation, wound healing and transwell assays were applied to demonstrate the effect of RBP4 on GC cell function. Flow cytometric detection of apoptosis after RBP4 knockdown. Nude mice xenograft model elucidates the role of RBP4 for GC in vivo. Related proteins of the RAS signaling pathway were analyzed by employing Western blot assays.
Results: RBP4 is highly expressed in GC. RBP4 is closely associated with patient survival and sensitivity to a wide range of antitumor agents. Knockdown of RBP4 promoted apoptosis and inhibited cell proliferation, invasion and migration. RBP4 promotes GC tumorigenesis in vivo. Finally, RBP4 modulates the RAS/RAF/ERK axis.
Conclusion: RBP4 may promote gastric carcinogenesis and development through the RAS/RAF/ERK axis and is expected to be a novel target for GC treatment.

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视黄醇结合蛋白 4 是一种潜在的肿瘤生物标记物，可促进胃癌的恶性行为

背景：胃癌（GC）是一种表型高度异质性的疾病，由多种因素引起。视黄醇结合蛋白 4（RBP4）是脂质转运蛋白家族中的一员，参与细胞间的物质转运，在多种癌症中起着至关重要的作用。然而，RBP4在GC中的表达和作用仍然未知：在这项研究中，我们利用基于网络的生物信息学工具探讨了 RBP4 在 GC 中的表达、预后意义、免疫微环境、药物反应性和相关信号通路的功能。免疫组化和实时定量 PCR 分析了 RBP4 在组织和细胞中的表达水平。应用 CCK-8、菌落形成、EDU掺入、伤口愈合和透孔试验来证明 RBP4 对 GC 细胞功能的影响。流式细胞术检测 RBP4 敲除后的细胞凋亡。裸鼠异种移植模型阐明了 RBP4 在体内对 GC 的作用。通过Western印迹法分析了RAS信号通路的相关蛋白：结果：RBP4在GC中高表达。RBP4与患者的存活率和对多种抗肿瘤药物的敏感性密切相关。敲除 RBP4 可促进细胞凋亡，抑制细胞增殖、侵袭和迁移。RBP4 在体内促进 GC 肿瘤的发生。最后，RBP4调节RAS/RAF/ERK轴：结论：RBP4 可通过 RAS/RAF/ERK 轴促进胃癌的发生和发展，有望成为治疗 GC 的新靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Management and Research Medicine-Oncology

CiteScore

7.40

自引率

0.00%

发文量

448

审稿时长

16 weeks

期刊介绍： Cancer Management and Research is an international, peer reviewed, open access journal focusing on cancer research and the optimal use of preventative and integrated treatment interventions to achieve improved outcomes, enhanced survival, and quality of life for cancer patients. Specific topics covered in the journal include: ◦Epidemiology, detection and screening ◦Cellular research and biomarkers ◦Identification of biotargets and agents with novel mechanisms of action ◦Optimal clinical use of existing anticancer agents, including combination therapies ◦Radiation and surgery ◦Palliative care ◦Patient adherence, quality of life, satisfaction The journal welcomes submitted papers covering original research, basic science, clinical & epidemiological studies, reviews & evaluations, guidelines, expert opinion and commentary, and case series that shed novel insights on a disease or disease subtype.