AUTHOR=Liu Jun , Lu Yi , Huang Wenan , He Zhibo 

TITLE=Comprehensive Analysis of Inhibitor of Apoptosis Protein Expression and Prognostic Significance in Non–Small Cell Lung Cancer

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.764270

DOI=10.3389/fgene.2021.764270

ISSN=1664-8021

ABSTRACT=<p>Inhibitors of apoptosis proteins (IAPs) have been associated with tumor development and progression by affecting apoptosis through cell death signaling pathways. To date, eight IAPs (BIRC1–8) have been identified in mammalian cells. However, the role of IAPs in non–small cell lung cancer (NSCLC) development and progression has not been explored in depth. In this study, we used public datasets and bioinformatics tools to compare the expression, prognostic significance, and function of IAPs in NSCLC and its subtypes. Expression of IAPs in cancer and normal tissues and at different stages of NSCLC was compared with gene expression profiling interactive analysis, and their prognostic significance was analyzed with the Kaplan–Meier Plotter database. The correlations among IAPs were analyzed with the STRING database and SPSS19.0. Functional annotation of IAPs was analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment on the basis of the DAVID tool. Among patients with lung adenocarcinoma (LUAD), the expression level of <italic>BIRC5</italic> was higher than that in normal samples, and the expression of <italic>BIRC1</italic> and <italic>BIRC5</italic> significantly varied in different stages. Moreover, the <italic>BIRC1</italic>–<italic>3</italic> and <italic>BIRC5</italic> mRNA levels were associated with overall survival (OS), and the <italic>BIRC1</italic>–<italic>2</italic> and <italic>BIRC5</italic>–<italic>6</italic> mRNA levels were associated with progression-free survival (PFS). Among patients with lung squamous cell carcinoma (LUSC), the expression level of <italic>BIRC1</italic> was lower and that of <italic>BIRC5</italic> was higher than those in normal tissues, and <italic>BIRC5</italic> expression significantly varied in different stages. <italic>BIRC1</italic> expression was associated with OS, whereas <italic>BIRC2</italic> and <italic>BIRC6</italic> expression was associated with PFS. Enrichment analysis showed that most IAPs are associated with ubiquitin- and apoptosis-related pathways. Collectively, this study suggests <italic>BIRC5</italic> as a potential diagnostic and staging marker, <italic>BIRC1</italic> as a potential marker of OS, and <italic>BIRC2</italic> and <italic>BIRC6</italic> as potential PFS markers for patients with NSCLC. These highlight new targets for the early detection, treatment, and management of NSCLC.</p>