1. Academic Validation
  2. Integrated analysis and validation reveal ACAP1 as a novel prognostic biomarker associated with tumor immunity in lung adenocarcinoma

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

  • Comput Struct Biotechnol J. 2022 Aug 13;20:4390-4401. doi: 10.1016/j.csbj.2022.08.026.
Ning Wang 1 Lingye Zhu 1 Xiaomei Xu 1 Chang Yu 2 Xiaoying Huang 1
Affiliations

Affiliations

  • 1 Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325000, PR China.
  • 2 Intervention Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, PR China.
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.

Keywords

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.

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