Department of Obstetrics and Gynecology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China.
DNA Cell Biol. 2020 Sep;39(9):1545-1557. doi: 10.1089/dna.2020.5596. Epub 2020 May 22.
ADP-ribosylation factor (Arf) GTPase-activating protein (GAP) with coiled-coil, ankyrin repeat and PH domains 1 (ACAP1) is an Arf6 GAP that regulates membrane trafficking and is critical for the migratory potential of cells. However, the roles of ACAP1 have not been fully explored and its association with clinicopathological features in ovarian cancer is still unknown. In this study, we systematically analyzed multiple databases, including TISIDB, Tumor Immune Estimation Resource (TIMER2.0), Gene Expression Omnibus (GEO), CORTECON, Kaplan-Meier Plotter and LinkedOmics platforms to reveal the clinical significance and function of ACAP1 in ovarian cancer. We found that the expression of ACAP1 was upregulated in ovarian cancer and high ACAP1 expression predicted poor prognosis. Our data demonstrated that the expression and methylation status of ACAP1 were strongly correlated with immune infiltration levels, immunomodulators, and chemokines. Gene set enrichment analysis (GSEA) analysis also showed that the mechanism of ACAP1 in regulating ovarian cancer was related to a variety of immune-related pathways. In addition, we also revealed that the expression of ACAP1 was altered during cell differentiation and associated with cancer cell stemness markers. Our study highlights the clinical significance of ACAP1 in ovarian cancer and provides insight into the novel function of ACAP1 in regulation of tumor immune microenvironment and cancer cell stemness.
ADP-核糖基化因子 (Arf) GTP 酶激活蛋白 (GAP) 与卷曲螺旋、锚蛋白重复和 PH 结构域 1 (ACAP1) 是一种 Arf6 GAP，可调节膜运输，对细胞的迁移潜能至关重要。然而，ACAP1 的作用尚未得到充分探索，其与卵巢癌临床病理特征的关联尚不清楚。在这项研究中，我们系统地分析了多个数据库，包括 TISIDB、肿瘤免疫估计资源 (TIMER2.0)、基因表达综合数据库 (GEO)、CORTECON、Kaplan-Meier Plotter 和 LinkedOmics 平台，以揭示 ACAP1 在卵巢癌中的临床意义和功能。我们发现 ACAP1 在卵巢癌中表达上调，高 ACAP1 表达预示着预后不良。我们的数据表明，ACAP1 的表达和甲基化状态与免疫浸润水平、免疫调节剂和趋化因子强烈相关。基因集富集分析 (GSEA) 分析还表明，ACAP1 调节卵巢癌的机制与多种免疫相关途径有关。此外，我们还揭示了 ACAP1 在细胞分化过程中的表达变化，并与癌症细胞干性标志物相关。我们的研究强调了 ACAP1 在卵巢癌中的临床意义，并为 ACAP1 调节肿瘤免疫微环境和癌症细胞干性的新功能提供了深入了解。
