Abstract
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 BIRC5 was higher than that in normal samples, and the expression of BIRC1 and BIRC5 significantly varied in different stages. Moreover, the BIRC1–3 and BIRC5 mRNA levels were associated with overall survival (OS), and the BIRC1–2 and BIRC5–6 mRNA levels were associated with progression-free survival (PFS). Among patients with lung squamous cell carcinoma (LUSC), the expression level of BIRC1 was lower and that of BIRC5 was higher than those in normal tissues, and BIRC5 expression significantly varied in different stages. BIRC1 expression was associated with OS, whereas BIRC2 and BIRC6 expression was associated with PFS. Enrichment analysis showed that most IAPs are associated with ubiquitin- and apoptosis-related pathways. Collectively, this study suggests BIRC5 as a potential diagnostic and staging marker, BIRC1 as a potential marker of OS, and BIRC2 and BIRC6 as potential PFS markers for patients with NSCLC. These highlight new targets for the early detection, treatment, and management of NSCLC.
Highlights
Non–small cell lung cancer (NSCLC) has one of the highest mortality rates among malignant tumors globally, which accounts for approximately 80% of all lung cancers (Siegel et al, 2020)
The Kaplan–Meier curve and associated statistical analyses revealed that decreased BIRC1–3 mRNA levels and increased BIRC5 mRNA levels were significantly associated with the overall survival (OS), whereas the decreased BIRC1-2 and 6 mRNA levels and the increased BIRC5 mRNA levels were significantly associated with the progression-free survival (PFS) of patients with lung adenocarcinoma (LUAD) (Table 2; Figure 3A)
A decreased BIRC1 mRNA level was significantly associated with OS, whereas increased BIRC2 and BIRC6 mRNA levels were significantly associated with the PFS of the patients with lung squamous cell carcinoma (LUSC) (Table 2; Figure 3B)
Summary
Non–small cell lung cancer (NSCLC) has one of the highest mortality rates among malignant tumors globally, which accounts for approximately 80% of all lung cancers (Siegel et al, 2020). The two predominant histological phenotypes of NSCLC are lung adenocarcinoma (LUAD, 50% of cases) and lung squamous cell carcinoma (LUSC, 40% of cases) (Davidson et al, 2013; Langer et al, 2015). The prognosis of NSCLC remains poor with a 5-year survival rate of only 2%–13% (Liu et al, 2020). The primary treatment of NSCLC is surgery, radiotherapy, and chemotherapy (Upadhya et al, 2021). The current biomarkers used to predict NSCLC prognosis have some limitations; it is necessary to explore new biomarkers as diagnostic and prognostic indicators to effectively improve survival and individualized treatment
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