关键词： ACAP1 ACAP1, ADP-ribosylation factor (Arf)-GTPase-activating protein (GAP) with coiled-coil, ankyrin repeat and PH domains 1 Arf6, ADP-ribosylation factor 6 CAMs, cell adhesion molecules CI, confidence interval DEGs, differentially expressed genes DSS, disease specific survival GEFs, guanine nucleotide exchange factors GEPIA, gene expression profiling interactive analysis GO, gene ontology GSEA, Gene Set Enrichment Analysis GTEx, genotype-tissue expression HR, hazard ratio ICB, immune checkpoint blockade Immune infiltrates Immunotherapy KEGG, Kyoto encyclopedia of genes and genomes LUAD, lung adenocarcinoma Lung adenocarcinoma OS, overall survival PD-1, programmed death receptor 1 PD-L1, programmed death receptor ligand 1 PPI, protein–protein interaction Prognosis TCGA, the cancer genome atlas TIME, tumor immune microenvironment TIMER, tumor immune estimation resource TME, tumor microenvironment qRT-PCR, quantitative reverse-transcription polymerase chain reaction ACAP1 ACAP1, ADP-ribosylation factor (Arf)-GTPase-activating protein (GAP) with coiled-coil, ankyrin repeat and PH domains 1 Arf6, ADP-ribosylation factor 6 CAMs, cell adhesion molecules CI, confidence interval DEGs, differentially expressed genes DSS, disease specific survival GEFs, guanine nucleotide exchange factors GEPIA, gene expression profiling interactive analysis GO, gene ontology GSEA, Gene Set Enrichment Analysis GTEx, genotype-tissue expression HR, hazard ratio ICB, immune checkpoint blockade Immune infiltrates Immunotherapy KEGG, Kyoto encyclopedia of genes and genomes LUAD, lung adenocarcinoma Lung adenocarcinoma OS, overall survival PD-1, programmed death receptor 1 PD-L1, programmed death receptor ligand 1 PPI, protein–protein interaction Prognosis TCGA, the cancer genome atlas TIME, tumor immune microenvironment TIMER, tumor immune estimation resource TME, tumor microenvironment qRT-PCR, quantitative reverse-transcription polymerase chain reaction

来  源：   DOI：10.1016/j.csbj.2022.08.026   PDF(Pubmed)

Abstract：
ADP-ribosylation factor (Arf)-GTPase-activating protein (GAP) with coiled-coil, ankyrin repeat and PH domains 1 (ACAP1) has been reported to serve as an adaptor for clathrin coat complex playing a role in endocytic recycling and cellular migration. The potential role of ACAP1 in lung adenocarcinoma (LUAD) has not been yet completely defined. We performed the comprehensive analyses, including gene expression, survival analysis, genetic alteration, function enrichment, and immune characteristics. ACAP1 was remarkably downregulated in tumor tissues, and linked with the clinicopathologic features in LUAD patients. Prognostic analysis demonstrated that low ACAP1 expression was correlated with unsatisfactory overall survival (OS) and disease specific survival (DSS) in LUAD patients. Moreover, ACAP1 could be determined as a prognostic biomarker according to Cox proportional hazard model and nomogram model. We also confirmed that ACAP1 was downregulated in two LUAD cell lines, comparing to normal lung cell. Overexpression of ACAP1 caused a profound attenuation in cell proliferation, migration, invasion, and promoted cell apoptosis. Additionally, functional enrichment analyses confirmed that ACAP1 was highly correlated with T cell activation and immune response. Then, we further conducted immune landscape analyses, including single cell RNA sequencing, immune cells infiltration, and immune checkpoints. ACAP1 expression was positively associated with the infiltrating level of immune cells in TME and the expression of immune checkpoint molecules. This study first comprehensively analyzed molecular expression, clinical implication, and immune landscape features of ACAP1 in LUAD, suggesting that ACAP1 was predictive of prognosis and could serve as a potential biomarker predicting immunotherapy response for LUAD patients.
摘要：
带卷曲螺旋的ADP-核糖基化因子(Arf)-GTP酶激活蛋白(GAP),据报道，锚蛋白重复序列和PH结构域1（ACAP1）可作为网格蛋白外套复合物的衔接子，在胞吞再循环和细胞迁移中起作用。ACAP1在肺腺癌（LUAD）中的潜在作用尚未完全确定。我们进行了全面的分析，包括基因表达，生存分析,遗传改变,功能富集，和免疫特性。ACAP1在肿瘤组织中显著下调,并与LUAD患者的临床病理特征有关。预后分析表明，低ACAP1表达与LUAD患者不满意的总生存期（OS）和疾病特异性生存期（DSS）相关。此外，ACAP1可以根据Cox比例风险模型和列线图模型确定为预后生物标志物。我们还证实ACAP1在两个LUAD细胞系中下调，与正常肺细胞相比。ACAP1的过表达导致细胞增殖的严重衰减，迁移,入侵,促进细胞凋亡。此外,功能富集分析证实ACAP1与T细胞活化和免疫应答高度相关.然后，我们进一步进行了免疫景观分析，包括单细胞RNA测序，免疫细胞浸润，和免疫检查点。ACAP1的表达与TME中免疫细胞的浸润水平和免疫检查点分子的表达呈正相关。本研究首先综合分析了分子表达,临床意义，以及LUAD中ACAP1的免疫景观特征，提示ACAP1可预测患者的预后,并可作为预测LUAD患者免疫治疗反应的潜在生物标志物.
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