Sun Aijun, Cai Fengze, Xiong Qingping, Xie Tong, Li Xiang, Xie Yanteng, Luo Ruiyang, Hu Wenwen, Zhong Fei, Wang Shiyan
Department of Thyroid and Breast Oncological Surgery, The Affiliated Huaian Hospital of Xuzhou Medical University and Huai'an Second People's Hospital, Huai'an, Jiangsu, China.
School of Life Science and Food Engineering, Huaiyin Institute of Technology, Huai'an, Jiangsu, China.
Front Mol Biosci. 2023 Oct 24;10:1277830. doi: 10.3389/fmolb.2023.1277830. eCollection 2023.
Abelson interactor Family Member 3 (ABI3) encodes protein that not only suppresses the ectopic metastasis of tumor cells but also hinders their migration. Although ABI3 had been found to modulate the advancement of diverse neoplasms, there is no comprehensive pan-cancer analysis of its effects. The transcriptomics data of neoplasm and normal tissues were retrieved from the Genomic Data Commons (GDC) data portal, and UCSC XENA database. To gather protein information for ABI3, Human Protein Atlas (HPA) and GeneMANIA websites were utilized. Additionally, Tumor Immune Single-cell Hub (TISCH) database was consulted to determine the primary cell types expressing ABI3 in cancer microenvironments. Univariate Cox regression approach was leveraged to evaluate ABI3's prognostic role across cancers. The Cbioportal and Gene Set Cancer Analysis (GSCA) website were leveraged to scrutinize the genomic landscape information across cancers. TIMER2.0 was leveraged to probe the immune cell infiltrations associated with ABI3 across cancers. The associations of ABI3 with immune-related genes were analyzed through Spearman correlation method. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were utilized to search associated biological pathways. The CellMiner database and molecular docking were implemented to identify potential interactions between the ABI3 protein and specific anticarcinogen. ABI3 expression and its ability to predict prognosis varied distinct tumor, with particularly high expression observed in Tprolif cells and monocytes/macrophages. Copy number variation (CNV) and methylation negatively correlated with ABI3 expression in the majority of malignancies. Corresponding mutation survival analysis indicated that the mutation status of ABI3 was strongly connected to the prognosis of LGG patients. ABI3 expression was linked to immunotherapeutic biomarkers and response in cancers. ESTIMATE and immune infiltrations analyses presented ABI3 association with immunosuppression. ABI3 was significantly correlated with immunoregulators and immune-related pathways. Lastly, prospective ABI3-targeted drugs were filtered and docked to ABI3 protein. Our study reveals that ABI3 acts as a robust tumor biomarker. Its functions are vital that could inhibit ectopic metastasis of tumor cells and modulate cellular adhesion and migration. The discoveries presented here may have noteworthy consequences for the creation of fresh anticancer suppressors, especially those targeting BRCA.
阿贝尔森相互作用蛋白家族成员3(ABI3)编码的蛋白质不仅能抑制肿瘤细胞的异位转移,还能阻碍其迁移。尽管已发现ABI3可调节多种肿瘤的进展,但其作用尚无全面的泛癌分析。肿瘤组织和正常组织的转录组学数据从基因组数据共享库(GDC)数据门户和UCSC XENA数据库中获取。为收集ABI3的蛋白质信息,利用了人类蛋白质图谱(HPA)和GeneMANIA网站。此外,还查阅了肿瘤免疫单细胞中心(TISCH)数据库,以确定在癌症微环境中表达ABI3的主要细胞类型。采用单变量Cox回归方法评估ABI3在各种癌症中的预后作用。利用Cbioportal和基因集癌症分析(GSCA)网站仔细研究各种癌症的基因组景观信息。利用TIMER2.0探究各种癌症中与ABI3相关的免疫细胞浸润情况。通过Spearman相关方法分析ABI3与免疫相关基因的关联。利用基因集富集分析(GSEA)和基因集变异分析(GSVA)搜索相关的生物学途径。利用CellMiner数据库和分子对接来确定ABI3蛋白与特定抗癌剂之间的潜在相互作用。ABI3的表达及其预测预后的能力在不同肿瘤中存在差异,在增殖性T细胞和单核细胞/巨噬细胞中观察到特别高的表达。在大多数恶性肿瘤中,拷贝数变异(CNV)和甲基化与ABI3表达呈负相关。相应的突变生存分析表明,ABI3的突变状态与低级别胶质瘤(LGG)患者的预后密切相关。ABI3表达与癌症中的免疫治疗生物标志物及反应相关。ESTIMATE和免疫浸润分析表明ABI3与免疫抑制有关。ABI3与免疫调节因子和免疫相关途径显著相关。最后,筛选出针对ABI3的前瞻性药物并与ABI3蛋白进行对接。我们的研究表明,ABI3是一种强大的肿瘤生物标志物。其功能至关重要,可抑制肿瘤细胞的异位转移并调节细胞黏附和迁移。本文的发现可能对新型抗癌抑制剂的研发产生显著影响,尤其是针对乳腺癌(BRCA)的抑制剂。