Integrated analysis and validation reveal ACAP1 as a novel prognostic biomarker associated with tumor immunity in lung adenocarcinoma

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...

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Main Authors: Ning Wang, Lingye Zhu, Xiaomei Xu, Chang Yu, Xiaoying Huang
Format: Article
Language:English
Published: Elsevier 2022-01-01
Series:Computational and Structural Biotechnology Journal
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2001037022003592
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author Ning Wang
Lingye Zhu
Xiaomei Xu
Chang Yu
Xiaoying Huang
author_facet Ning Wang
Lingye Zhu
Xiaomei Xu
Chang Yu
Xiaoying Huang
author_sort Ning Wang
collection DOAJ
description 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.
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spelling doaj.art-d61c64a539c04b7d88d08527399342b82022-12-24T04:53:57ZengElsevierComputational and Structural Biotechnology Journal2001-03702022-01-012043904401Integrated analysis and validation reveal ACAP1 as a novel prognostic biomarker associated with tumor immunity in lung adenocarcinomaNing Wang0Lingye Zhu1Xiaomei Xu2Chang Yu3Xiaoying Huang4Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325000, PR ChinaDivision of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325000, PR ChinaDivision of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325000, PR ChinaIntervention Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, PR China; Corresponding authors.Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325000, PR China; Corresponding authors.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.http://www.sciencedirect.com/science/article/pii/S2001037022003592ACAP1Lung adenocarcinomaPrognosisImmune infiltratesImmunotherapy
spellingShingle Ning Wang
Lingye Zhu
Xiaomei Xu
Chang Yu
Xiaoying Huang
Integrated analysis and validation reveal ACAP1 as a novel prognostic biomarker associated with tumor immunity in lung adenocarcinoma
Computational and Structural Biotechnology Journal
ACAP1
Lung adenocarcinoma
Prognosis
Immune infiltrates
Immunotherapy
title Integrated analysis and validation reveal ACAP1 as a novel prognostic biomarker associated with tumor immunity in lung adenocarcinoma
title_full Integrated analysis and validation reveal ACAP1 as a novel prognostic biomarker associated with tumor immunity in lung adenocarcinoma
title_fullStr Integrated analysis and validation reveal ACAP1 as a novel prognostic biomarker associated with tumor immunity in lung adenocarcinoma
title_full_unstemmed Integrated analysis and validation reveal ACAP1 as a novel prognostic biomarker associated with tumor immunity in lung adenocarcinoma
title_short Integrated analysis and validation reveal ACAP1 as a novel prognostic biomarker associated with tumor immunity in lung adenocarcinoma
title_sort integrated analysis and validation reveal acap1 as a novel prognostic biomarker associated with tumor immunity in lung adenocarcinoma
topic ACAP1
Lung adenocarcinoma
Prognosis
Immune infiltrates
Immunotherapy
url http://www.sciencedirect.com/science/article/pii/S2001037022003592
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AT xiaomeixu integratedanalysisandvalidationrevealacap1asanovelprognosticbiomarkerassociatedwithtumorimmunityinlungadenocarcinoma
AT changyu integratedanalysisandvalidationrevealacap1asanovelprognosticbiomarkerassociatedwithtumorimmunityinlungadenocarcinoma
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